IL-10 (Interleukin-10, also known as Cytokine Synthesis Inhibitory Factor/CSIF) is the prototypical anti-inflammatory cytokine and founding member of the IL-10 family. It is a secreted homodimeric four-helix-bundle cytokine (~36 kDa dimer) that signals through a heterotetrameric receptor complex comprising two IL-10RA (ligand-binding) and two IL-10RB (signal-transducing) chains. Receptor engagement activates JAK1 (via IL-10RA) and TYK2 (via IL-10RB), leading to STAT3 phosphorylation, dimerization, nuclear translocation, and transcription of anti-inflammatory target genes (e.g., SOCS3, IL1RN). IL-10 is produced by multiple immune cell types including monocytes/macrophages, dendritic cells, T cell subsets (Th1, Th2, Treg), B cells, and NK cells. Its principal function is to suppress inflammatory responses by inhibiting pro-inflammatory cytokine production (TNF, IL-1, IL-6, IL-8, IL-12) in monocytes/macrophages, downregulating MHC class II expression and co-stimulatory molecules, and limiting T cell activation. IL-10 also has immunostimulatory effects on B cells (promoting proliferation, differentiation, and immunoglobulin production) and CD8+ T cells in certain contexts. Loss-of-function mutations in IL10 or IL10R cause very-early-onset inflammatory bowel disease (VEO-IBD), establishing IL-10 signaling as essential for intestinal immune homeostasis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006955 immune response | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for immune response. IL-10 is a central immunomodulatory cytokine involved in both innate and adaptive immune responses. The phylogenetic inference is well-supported by extensive literature on IL-10 across vertebrates. Reason: IL-10 is definitively involved in immune response; this is one of its most fundamental roles. The IBA annotation is well-supported by conserved function across vertebrate IL-10 orthologs and extensive experimental evidence in human, mouse, rat, and zebrafish (PMID:1940799, deep research review). |
| GO:0005125 cytokine activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for cytokine activity. IL-10 is a prototypical cytokine that signals through the IL-10 receptor complex to activate JAK-STAT signaling. Reason: Cytokine activity is the core molecular function of IL-10. It is the founding member of the IL-10 cytokine family and signals through its receptor complex to mediate its biological effects. This is well-established across all orthologs (PMID:1940799, UniProt P22301). |
| GO:0005615 extracellular space | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for extracellular space localization. IL-10 is a secreted cytokine that functions in the extracellular space by binding cell-surface receptors. Reason: IL-10 contains a signal peptide (residues 1-18) and is secreted. It functions as a soluble homodimer in the extracellular space where it engages the IL-10R complex on target cells (UniProt P22301, deep research review). |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for positive regulation of JAK-STAT signaling. IL-10 signals through JAK1/TYK2 to activate STAT3 phosphorylation. Reason: This is a core aspect of IL-10 signaling. Binding to IL-10RA/IL-10RB activates JAK1 and TYK2, leading to STAT3 phosphorylation, which is the canonical downstream signaling pathway (PMID:16982608, deep research review). |
| GO:0050728 negative regulation of inflammatory response | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for negative regulation of inflammatory response. IL-10 is the prototypical anti-inflammatory cytokine. Reason: This is the single most characteristic function of IL-10. It suppresses pro-inflammatory cytokine production, downregulates MHC class II, and limits inflammatory responses. Conserved across vertebrate orthologs (PMID:1940799, PMID:10443688, deep research review). |
| GO:0140105 interleukin-10-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for IL-10-mediated signaling pathway. IL-10 is the ligand that initiates this pathway. Reason: IL-10 is the defining ligand for the IL-10-mediated signaling pathway. This is essentially tautological for the IL-10 protein itself and well-supported by phylogenetic inference (deep research review). |
| GO:0005125 cytokine activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for cytokine activity, consistent with the IBA annotation and multiple IDA annotations for the same term. Reason: Redundant with IBA and IDA annotations but correct. IL-10 is unambiguously a cytokine (UniProt P22301, PMID:1940799). |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for extracellular region. IL-10 is a secreted protein. Reason: Broader than extracellular space (GO:0005615) but still correct. IL-10 is secreted and functions in the extracellular region (UniProt P22301). |
| GO:0005615 extracellular space | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for extracellular space, consistent with IBA annotation. Reason: Redundant with IBA annotation but correct. IL-10 is a secreted cytokine found in extracellular space (UniProt P22301). |
| GO:0006955 immune response | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for immune response, consistent with IBA annotation. Reason: Redundant with IBA annotation but correct. IL-10 is a key immune response cytokine (PMID:1940799). |
| GO:0005515 protein binding | IPI PMID:11485736 Crystal structure of the IL-10/IL-10R1 complex reveals a sha... | MODIFY | Summary: IPI protein binding annotation with UniProtKB:Q13651 (IL-10RA) as the partner. PMID:11485736 is the 2.9 A crystal structure of the IL-10/soluble IL-10R1 complex (two IL-10 molecules and four sIL-10R1 molecules), directly establishing the receptor-binding interface and showing that IL-10R1 and IL-10R2 recognize the same site on IL-10. Reason: The interaction between IL-10 and IL-10RA is physiologically critical and well-characterized, but "protein binding" is too vague. This should be annotated as interleukin-10 receptor binding (GO:0005141) which more precisely captures the functional nature of this interaction. Proposed replacements: interleukin-10 receptor binding Supporting Evidence: PMID:11485736 Interleukin 10 (IL-10) is a dimeric cytokine that plays a central role in suppressing inflammatory responses. These activities are dependent on the interaction of IL-10 with its high-affinity receptor (IL-10R1). |
| GO:0005515 protein binding | IPI PMID:12513909 Comparison of interleukin-22 and interleukin-10 soluble rece... | MODIFY | Summary: IPI protein binding based on interaction with IL-10RB (Q08334) and IL-10RA (Q13651). PMID:12513909 compares IL-22 and IL-10 soluble receptor complexes. Reason: IL-10 binds both IL-10RA and IL-10RB as part of its receptor complex. "Protein binding" is uninformative; should be interleukin-10 receptor binding (GO:0005141). Proposed replacements: interleukin-10 receptor binding Supporting Evidence: PMID:12513909 IL-22 and IL-10 require different ligand-specific receptor chains (IL-22R and IL-10R1) but share a second receptor chain (IL-10R2) to initiate cellular responses. |
| GO:0005515 protein binding | IPI PMID:15837194 Same structure, different function crystal structure of the ... | MODIFY | Summary: IPI protein binding with UniProtKB:Q13651 (IL-10RA) as the partner. PMID:15837194 is the crystal structure of Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain, which characterizes the same IL-10 / IL-10R1 binding surface used by human IL-10 and quantifies the ~1000-fold affinity difference between the viral and human ligands for IL-10R1. Reason: The interaction being recorded is IL-10 with its high-affinity receptor chain IL-10RA, so the uninformative GO:0005515 should be replaced by GO:0005141 (interleukin-10 receptor binding), which names the actual molecular function. Proposed replacements: interleukin-10 receptor binding Supporting Evidence: PMID:15837194 These functional differences have been correlated with the approximately 1000-fold lower affinity of vIL-10, compared to hIL-10, for the IL-10R1 receptor chain. |
| GO:0005515 protein binding | IPI PMID:20462497 Structure and mechanism of receptor sharing by the IL-10R2 c... | MODIFY | Summary: IPI protein binding from PMID:20462497, which describes the structure and mechanism of receptor sharing by IL-10R2 (IL-10RB) common chain. Interaction with Q08334 (IL-10RB) and Q13651 (IL-10RA). Reason: This paper provides structural evidence for IL-10 binding its receptor chains. Should be annotated as interleukin-10 receptor binding (GO:0005141). Proposed replacements: interleukin-10 receptor binding Supporting Evidence: PMID:20462497 IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome | REMOVE | Summary: IPI protein binding from the HuRI (Human Reference Interactome) high-throughput yeast two-hybrid study (PMID:32296183). The six recorded partners were checked against UniProt and are O76003 (GLRX3, cytosolic glutaredoxin-3), P0DPK4 (NOTCH2NLC), P25490 (YY1, a nuclear transcriptional repressor), and three keratin-associated proteins P60410 (KRTAP10-8), Q8IUG1 (KRTAP1-3) and Q9BYQ7 (KRTAP4-1). All six are intracellular or nuclear/hair-shaft proteins that a secreted cytokine acting on cell-surface IL-10RA/IL-10RB would never encounter in vivo. Reason: PMID:32296183 is a systematic all-by-all Y2H screen in which both partners are expressed in the yeast nucleus, so a secreted, disulfide-bonded four-helix-bundle cytokine is tested outside its native compartment and outside its native folding environment. KRTAP proteins in particular are well-known frequent-flier Y2H artifacts. None of the six partners is corroborated by any low-throughput study, and none has a compartment overlapping the extracellular space where IL-10 acts (PMID:24994464, PMID:21323571). This is a false-positive interaction set rather than evidence of an IL-10 molecular function. Supporting Evidence: PMID:32296183 we expect HuRI to be depleted for PPIs that depend on post-translational processing of human proteins that the yeast cell is unable to catalyze or that require additional partners to stabilize the interaction |
| GO:0005515 protein binding | IPI PMID:16982608 Conformational changes mediate interleukin-10 receptor 2 (IL... | MODIFY | Summary: IPI protein binding with UniProtKB:Q13651 (IL-10RA) as the partner. PMID:16982608 maps the IL-10R2 binding site on IL-10 by surface plasmon resonance and cell-based assays, locating the critical IL-10R2 contact residues in helix A adjacent to the IL-10R1 recognition surface, and shows the ternary complex assembles sequentially with IL-10 / IL-10R1 engagement preceding IL-10R2 recruitment. Reason: The measured interactions are of IL-10 with its own receptor chains (IL-10RA and, in the same study, IL-10RB), so GO:0005141 (interleukin-10 receptor binding) replaces the uninformative GO:0005515 and captures the actual molecular function. Proposed replacements: interleukin-10 receptor binding Supporting Evidence: PMID:16982608 Interleukin-10 receptor 2 (IL-10R2) is a critical component of the IL-10.IL-10R1.IL-10R2 complex which regulates IL-10-mediated immunomodulatory responses. |
| GO:0001818 negative regulation of cytokine production | IEA GO_REF:0000107 | ACCEPT | Summary: IEA transfer from rat Il10 (P29456). IL-10 is well-established as a negative regulator of cytokine production. Reason: This is a core function of IL-10. It was originally named Cytokine Synthesis Inhibitory Factor (CSIF) precisely because it inhibits cytokine production by monocytes (PMID:1940799). The IEA transfer is well-supported. |
| GO:0001938 positive regulation of endothelial cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from mouse Il10 (P18893) for positive regulation of endothelial cell proliferation. This is a non-immune pleiotropic effect. Reason: While IL-10 has been reported to have effects on endothelial cells, this is a downstream pleiotropic effect rather than a core function. IL-10 is primarily an immune regulatory cytokine. The annotation represents an over-annotation of a secondary effect observed in specific experimental conditions. |
| GO:0005141 interleukin-10 receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA transfer from rat Il10 (P29456). IL-10 receptor binding is the primary molecular function through which IL-10 initiates signaling. Reason: IL-10 receptor binding is a core molecular function. IL-10 binds the IL-10RA/IL-10RB receptor complex to initiate downstream JAK-STAT signaling (UniProt P22301, deep research review). |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from mouse Il10 (P18893). IL-10 can inhibit proliferation of certain cell types including T cells and some other cell populations. Reason: IL-10 can inhibit T cell proliferation (PMID:8499633) and has anti-proliferative effects on some cell types, but this is a broad term that does not capture the specific immune regulatory context. Acceptable as a non-core annotation. Supporting Evidence: PMID:8499633 Human interleukin-10 (IL-10) inhibits T-cell proliferation and cytokine production in the presence of monocytes. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 expression may be induced by xenobiotic stimuli in rats, but this is not a core function for human IL-10. Reason: Response to xenobiotic stimulus is a peripheral observation likely from rodent studies where IL-10 expression was measured after xenobiotic exposure. This does not represent a core function of IL-10 as a cytokine and is an over-annotation from ortholog transfer. |
| GO:0014823 response to activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 levels may change with physical activity in rats, but this is not a core function. Reason: Response to activity (physical exercise) is a peripheral observation. IL-10 levels may change as part of general immune modulation during exercise, but this does not represent a core function of the cytokine itself. |
| GO:0014854 response to inactivity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). Similar to response to activity, this is a peripheral observation. Reason: Response to inactivity is a peripheral observation from rodent studies. Not a core function of IL-10 as an anti-inflammatory cytokine. |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from rat Il10 (P29456). IL-10 is induced by LPS and also modulates the response to LPS. Reason: IL-10 is both induced by LPS stimulation and acts to suppress LPS-induced inflammatory responses. This is a well-established aspect of IL-10 biology (PMID:14971032, PMID:10443688), though it represents a stimulus-response context rather than core function per se. |
| GO:0032720 negative regulation of tumor necrosis factor production | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for negative regulation of TNF production. IL-10 is a potent suppressor of TNF production by monocytes/macrophages. Reason: Suppression of TNF production was one of the earliest identified functions of IL-10 (PMID:1940799) and is a core anti-inflammatory activity. The TAS annotation from PMID:19262501 also supports this. This IEA annotation is correct. |
| GO:0032868 response to insulin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 levels may be affected by insulin in metabolic contexts. Reason: Response to insulin is a peripheral metabolic observation from rodent studies. While there are links between IL-10 and metabolic regulation, this is not a core function of IL-10 as an immune cytokine. |
| GO:0034115 negative regulation of heterotypic cell-cell adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from mouse Il10 (P18893). IL-10 can downregulate adhesion molecules such as ICAM-1 on monocytes. Reason: IL-10 downregulates ICAM-1 and other adhesion molecules on monocytes (PMID:7512027 per UniProt), which affects cell-cell adhesion. This is a downstream consequence of IL-10's anti-inflammatory program rather than a core function, but it is a real effect. |
| GO:0034465 response to carbon monoxide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 expression may be induced by carbon monoxide in rat models. Reason: Response to carbon monoxide is a highly peripheral observation from rodent studies. This is not a core function of IL-10 and represents an over-annotation via ortholog transfer. |
| GO:0043032 positive regulation of macrophage activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA ortholog transfer from rat Il10 (UniProtKB:P29456). The rat source annotation was traced in QuickGO and is an IDA supported by PMID:25837415, in which IL-10 immobilised on nanofibre scaffolds and implanted around rat sciatic nerve drove macrophages toward the alternatively activated (M2) state, scored by ED1/arginase-1 and ED1/CD206 double labelling. This resolves the apparent contradiction with IL-10's better-known suppression of classically activated macrophages, because GO:0042116 (macrophage activation) is defined broadly as a change in morphology and behavior of a macrophage resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor, which encompasses alternative (M2) activation. No GO term for alternative macrophage activation exists, so GO:0043032 is the closest available term and there is no better MODIFY target. Reason: The transfer is biologically sound rather than contradictory - the underlying rat IDA (PMID:25837415) demonstrates IL-10-driven M2 polarization, and the GO definition of macrophage activation is broad enough to include it. However, this is a downstream cellular consequence of IL-10 / IL-10R / STAT3 signalling in myeloid cells rather than a core function of the cytokine, and stated without the M2 qualifier the term is easy to misread as promoting classical activation, which IL-10 potently suppresses (PMID:1940799). Keep as non-core. Supporting Evidence: PMID:25837415 Interleukin 10 (IL-10) is a cytokine that promotes macrophages toward an anti-inflammatory/wound healing state (M2 phenotype). PMID:25837415 IL-10 conjugated nanofibres successfully induced macrophage polarisation towards the M2 activated state within the scaffold material as well as the adjacent tissue surrounding the nerve. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from rat Il10 (P29456). IL-10 can inhibit apoptosis in certain cell types. Reason: IL-10 has been shown to inhibit apoptosis in T cells starved of IL-2 (PMID:8312229) and can promote survival of certain immune cell types. This is a real but non-core effect of IL-10 signaling. Supporting Evidence: PMID:8312229 IL-10 inhibits apoptotic cell death in human T cells starved of IL-2. |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 has been reported to have neuroprotective effects in certain rodent models. Reason: Neuroprotective effects of IL-10 have been observed in rodent models of neuroinflammation, but this is a highly context-dependent downstream effect rather than a core function of this immune cytokine. Over-annotation via ortholog transfer. |
| GO:0045019 negative regulation of nitric oxide biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from rat Il10 (P29456). IL-10 suppresses iNOS expression and NO production in activated macrophages. Reason: IL-10 suppresses iNOS expression and nitric oxide production as part of its anti-inflammatory program in macrophages. This is a documented downstream effect of IL-10-mediated suppression of inflammatory gene expression, though not a core molecular function. |
| GO:0045787 positive regulation of cell cycle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from mouse Il10 (P18893). IL-10 can promote cell cycle progression in certain cell types. Reason: While IL-10 can promote proliferation of certain cell types (e.g., B cells, mast cells), a generic "positive regulation of cell cycle" annotation is over-broad and does not capture the specific immune context. This is an over-annotation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from mouse Il10 (P18893). IL-10 signaling leads to STAT3-dependent transcriptional activation of anti-inflammatory genes. Reason: IL-10 does activate transcription of specific genes via STAT3, but this is an extremely broad GO term. It is technically correct as a downstream effect of IL-10 signaling but not informative about IL-10's specific function. |
| GO:0050807 regulation of synapse organization | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 has been implicated in neuroimmune contexts. Reason: Regulation of synapse organization is a very peripheral observation from rodent neuroimmune studies. This is not a core function of IL-10 as an immune cytokine and represents an over-annotation via ortholog transfer. |
| GO:0051384 response to glucocorticoid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from rat Il10 (P29456). Glucocorticoids can regulate IL-10 expression. Reason: IL-10 expression is known to be regulated by glucocorticoids (also supported by IDA annotation from PMID:10443688). While this describes regulation of IL-10 rather than a function of IL-10, the annotation is not wrong per se. Keep as non-core. |
| GO:0071392 cellular response to estradiol stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 levels may respond to estradiol in rodent studies. Reason: Response to estradiol is a peripheral hormonal regulation observation from rodent studies. Not a core function of IL-10. |
| GO:0097421 liver regeneration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from rat Il10 (P29456). IL-10 may play a role in liver regeneration in rodent models. Reason: Liver regeneration is a highly tissue-specific and peripheral observation. While IL-10 may be expressed during liver regeneration, this is not a core function of this immune cytokine. |
| GO:1903034 regulation of response to wounding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transfer from mouse Il10 (P18893). IL-10 modulates wound healing by regulating inflammatory responses. Reason: IL-10 does modulate wound healing through its anti-inflammatory properties, which is an extension of its core immune regulatory function. Keep as non-core since it is a contextual application of the core function. |
| GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from mouse Il10 (P18893). Highly specific neuroprotective annotation from rodent models. Reason: This is an extremely specific neuroprotective annotation from mouse studies. IL-10 is not a neuron-specific factor; this represents a highly contextual observation from specific experimental paradigms that does not reflect a core function. |
| GO:1903672 positive regulation of sprouting angiogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from mouse Il10 (P18893). IL-10 has been implicated in angiogenesis regulation. Reason: Regulation of angiogenesis is a downstream pleiotropic effect rather than a core function of IL-10 as an immune cytokine. Over-annotation from ortholog transfer. |
| GO:1904706 negative regulation of vascular associated smooth muscle cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA transfer from mouse Il10 (P18893). IL-10 may inhibit vascular smooth muscle cell proliferation. Reason: Vascular smooth muscle cell proliferation regulation is a peripheral non-immune effect. Over-annotation from ortholog transfer. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:7749983 Cross-linking of OX40 ligand, a member of the TNF/NGF cytoki... | KEEP AS NON CORE | Summary: IDA annotation from PMID:7749983. This paper is about OX40L (TNFSF4), not about IL-10, so the reference is misattributed. However, IL-10 signaling through STAT3 does activate transcription of target genes, so the annotation itself is not wrong -- it is just a very broad term. Consistent with the IEA annotation for the same term which is marked KEEP_AS_NON_CORE. Reason: The reference PMID:7749983 is misattributed (it describes OX40L cross-linking on murine B cells, not IL-10). Nevertheless, IL-10 does positively regulate transcription by RNA polymerase II via STAT3 signaling (PMID:16982608), so the annotation is biologically correct though overly broad. This is consistent with the IEA annotation for the same GO term. Kept as non-core because the term does not capture IL-10's specific function. Supporting Evidence: PMID:7749983 OX40 is a member of the TNF/NGF-receptor family expressed on activated T cells, whose ligand is found on activated T and B cells |
| GO:0140105 interleukin-10-mediated signaling pathway | IDA PMID:7749983 Cross-linking of OX40 ligand, a member of the TNF/NGF cytoki... | ACCEPT | Summary: IDA annotation from PMID:7749983. The reference is misattributed (paper is about OX40L/TNFSF4, not IL-10). However, IL-10 is the defining ligand for the IL-10-mediated signaling pathway, so the annotation itself is correct and well-supported by IBA, IDA from PMID:10443688, and IDA from PMID:24994464. Reason: IL-10 is the defining ligand for the IL-10-mediated signaling pathway; this is a core function that is essentially tautological. The reference PMID:7749983 is misattributed (it describes OX40L cross-linking on murine B cells), but the annotation is strongly supported by multiple other evidence lines including IBA (GO_REF:0000033), IDA (PMID:10443688), and IDA (PMID:24994464). Accepting the annotation despite the reference error because the biology is unambiguous. Supporting Evidence: PMID:7749983 OX40 is a member of the TNF/NGF-receptor family expressed on activated T cells, whose ligand is found on activated T and B cells |
| GO:0140105 interleukin-10-mediated signaling pathway | IDA PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | ACCEPT | Summary: IDA annotation for IL-10-mediated signaling pathway from PMID:10443688. This publication is not available for review but is frequently cited for IL-10 annotations and is likely a primary study of IL-10 signaling. Reason: IL-10 is the defining ligand for the IL-10-mediated signaling pathway. This PMID is cited for multiple IL-10 annotations and appears to be a key primary study. The annotation is consistent with the known biology of IL-10. Supporting Evidence: PMID:10443688 interleukin (IL)-10 (an anti-inflammatory cytokine) to differentially regulate the sensitivity of human monocytes/macrophages to glucocorticoids. |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IDA PMID:16982608 Conformational changes mediate interleukin-10 receptor 2 (IL... | ACCEPT | Summary: IDA annotation for positive regulation of JAK-STAT signaling from PMID:16982608. This paper likely describes the structural basis of IL-10 signaling through its receptor complex to activate JAK1/TYK2/STAT3. Reason: This is a core aspect of IL-10 function. IL-10 engagement of IL-10RA/IL-10RB activates JAK1 and TYK2, leading to STAT3 phosphorylation. PMID:16982608 is cited multiple times for IL-10 receptor and signaling annotations, suggesting it is a key structural/functional study (deep research review). Supporting Evidence: PMID:16982608 The ternary IL-10 signaling complex is assembled in a sequential order with the IL-10.IL-10R1 interaction occurring first followed by engagement of the IL-10R2 chain. |
| GO:0050864 regulation of B cell activation | IDA PMID:35443184 Human IL-10-producing B cells have diverse states that are i... | KEEP AS NON CORE | Summary: IDA annotation for regulation of B cell activation from PMID:35443184. IL-10 has well-established effects on B cells. Reason: IL-10 regulates B cell activation, which is a real but non-core function relative to its primary anti-inflammatory role. IL-10 was originally characterized as a B cell growth factor as well as a cytokine synthesis inhibitor (PMID:9184696, deep research review). Keep as non-core. Supporting Evidence: PMID:35443184 Regulatory B cells (Bregs) suppress immune responses through the secretion of interleukin-10 (IL-10). This immunomodulatory capacity holds therapeutic potential, yet a definitional immunophenotype for enumeration and prospective isolation of B cells capable of IL-10 production remains elusive. |
| GO:0005125 cytokine activity | IDA PMID:24994464 Low IL10 serum levels as key factor for predicting the susta... | ACCEPT | Summary: IDA annotation for cytokine activity from PMID:24994464 (about IL10 serum levels in HCV patients). This confirms IL-10 functions as a circulating cytokine. Reason: Cytokine activity is the core molecular function of IL-10. Multiple lines of evidence support this (PMID:1940799, PMID:24994464, IBA, IEA). Supporting Evidence: PMID:24994464 the levels of IL10 seem to influence response to IFNΞ±/RIB therapy. |
| GO:0005615 extracellular space | IDA PMID:24994464 Low IL10 serum levels as key factor for predicting the susta... | ACCEPT | Summary: IDA for extracellular space from PMID:24994464 (IL10 serum levels). Reason: IL-10 is a secreted cytokine detected in serum/plasma. Extracellular space localization is well-established. Supporting Evidence: PMID:24994464 IL10 serum levels could be further explored as a useful algorithm for identify the CT/TT SVR patients. |
| GO:0140105 interleukin-10-mediated signaling pathway | IDA PMID:24994464 Low IL10 serum levels as key factor for predicting the susta... | ACCEPT | Summary: IDA for IL-10-mediated signaling pathway from PMID:24994464. Reason: IL-10 is the defining ligand for IL-10-mediated signaling. This is a core annotation well-supported by multiple evidence lines. Supporting Evidence: PMID:24994464 the levels of IL10 seem to influence response to IFNΞ±/RIB therapy. |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:23071313 IL-10-induced microRNA-187 negatively regulates TNF-Ξ±, IL-6,... | KEEP AS NON CORE | Summary: IDA annotation for cellular response to LPS from PMID:23071313. IL-10 is both induced by and modulates the cellular response to LPS. Reason: IL-10 modulates the cellular response to LPS by suppressing pro-inflammatory cytokine production. This is a well-established aspect of IL-10 biology but represents a specific stimulus-response context rather than core function. Supporting Evidence: PMID:23071313 IL-10 is a potent anti-inflammatory molecule that, in phagocytes, negatively targets cytokine expression at transcriptional and posttranscriptional levels. |
| GO:1902895 positive regulation of miRNA transcription | IDA PMID:23071313 IL-10-induced microRNA-187 negatively regulates TNF-Ξ±, IL-6,... | KEEP AS NON CORE | Summary: IDA annotation for positive regulation of miRNA transcription from PMID:23071313. IL-10 has been shown to regulate miRNA expression as part of its signaling. Reason: IL-10 signaling through STAT3 can regulate miRNA transcription as a downstream effect. This is a mechanistic detail of IL-10 signaling rather than a core function, but it is experimentally supported. Keep as non-core. Supporting Evidence: PMID:23071313 we identify miR-187 as an IL-10-dependent miRNA playing a role in IL-10-mediated suppression of TNF-Ξ±, IL-6, and the p40 subunit of IL-12 (IL-12p40) produced by primary human monocytes following activation of Toll-like receptor 4 (TLR4). |
| GO:0050728 negative regulation of inflammatory response | IDA PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | ACCEPT | Summary: IDA annotation for negative regulation of inflammatory response from PMID:10443688. This is a core function of IL-10. Reason: This is the single most important function of IL-10. The anti-inflammatory activity of IL-10 has been demonstrated in numerous experimental systems (PMID:1940799, PMID:10443688, deep research review). Supporting Evidence: PMID:10443688 IL-10 acts synergistically with glucocorticoids. This is accompanied by opposite glucocorticoid receptor changes, respectively opposing and favoring glucocorticoid actions. |
| GO:0001818 negative regulation of cytokine production | IDA PMID:1940799 Interleukin 10(IL-10) inhibits cytokine synthesis by human m... | ACCEPT | Summary: IDA annotation for negative regulation of cytokine production from PMID:1940799. This is the seminal paper by de Waal Malefyt et al. (1991) establishing IL-10 as a cytokine synthesis inhibitor. Reason: This is one of the most fundamental annotations for IL-10. PMID:1940799 demonstrated that IL-10 inhibits cytokine synthesis by human monocytes. IL-10 was originally named Cytokine Synthesis Inhibitory Factor (CSIF) based on this activity. Supporting Evidence: PMID:1940799 Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. |
| GO:0010507 negative regulation of autophagy | IDA PMID:26962683 IL10 inhibits starvation-induced autophagy in hypertrophic s... | KEEP AS NON CORE | Summary: IDA annotation for negative regulation of autophagy from PMID:26962683, which showed IL-10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via STAT3/AKT-mTOR signaling crosstalk. Reason: IL-10 has been shown to inhibit autophagy in hypertrophic scar fibroblasts via crosstalk between IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways (PMID:26962683). This is a real but highly context-specific effect, not a core function of IL-10. Supporting Evidence: PMID:26962683 IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways. |
| GO:0045347 negative regulation of MHC class II biosynthetic process | IDA PMID:1940799 Interleukin 10(IL-10) inhibits cytokine synthesis by human m... | ACCEPT | Summary: IDA annotation for negative regulation of MHC class II biosynthetic process from PMID:1940799. IL-10 downregulates MHC class II expression on monocytes. Reason: IL-10 downregulation of MHC class II expression on monocytes and macrophages is a core function directly related to its immune suppressive activity (PMID:1940799, PMID:8144879 per UniProt, deep research review). Supporting Evidence: PMID:1940799 Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. |
| GO:0046983 protein dimerization activity | IDA PMID:16982608 Conformational changes mediate interleukin-10 receptor 2 (IL... | ACCEPT | Summary: IDA annotation for protein dimerization activity from PMID:16982608. IL-10 functions as a homodimer. Reason: IL-10 forms a non-covalent homodimer as its biologically active form. The dimer is stabilized by domain swapping and intrachain disulfide bonds. This is well-established from crystal structures and biochemical studies (UniProt P22301, PMID:8364028, deep research review). Supporting Evidence: PMID:16982608 These studies highlight the importance of structure in regulating low affinity protein-protein interactions and IL-10 signal transduction. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:16606666 B7-H4 expression identifies a novel suppressive macrophage p... | KEEP AS NON CORE | Summary: IDA annotation for positive regulation of transcription from PMID:16606666. IL-10 signaling through STAT3 activates transcription of target genes. Reason: IL-10 does activate transcription via STAT3 signaling. This is technically correct but is a very broad term. The specific transcriptional effects (anti-inflammatory gene induction) are better captured by other annotations. Keep as non-core. Supporting Evidence: PMID:16606666 Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:17875732 Relationship between B7-H4, regulatory T cells, and patient ... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of transcription from PMID:17875732. This paper showed that tumor Treg cells enable macrophages to produce IL-10 and IL-6, and that tumor macrophages stimulate B7-H4 expression in an autocrine manner through IL-10 and IL-6. IL-10 thus indirectly promotes transcription of B7-H4 in this tumor microenvironment context. Reason: PMID:17875732 demonstrates that IL-10 (produced by Treg-stimulated macrophages) stimulates B7-H4 expression on macrophages in ovarian carcinoma, which constitutes positive regulation of transcription. This is consistent with IL-10's known ability to activate STAT3-dependent gene transcription and with the IDA annotation for the same term (GO:0045893) from PMID:16606666, which is also marked KEEP_AS_NON_CORE. The transcriptional regulation is a downstream consequence of IL-10 signaling rather than a core function. Supporting Evidence: PMID:17875732 Tumor Treg cells enabled macrophages to spontaneously produce interleukin (IL)-10 and IL-6. Tumor macrophages stimulated B7-H4 expression in an autocrine manner through IL-10 and IL-6. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | NAS PMID:33737461 Structure-based decoupling of the pro- and anti-inflammatory... | ACCEPT | Summary: NAS annotation for JAK-STAT signaling from PMID:33737461 (ComplexPortal). IL-10 signals through its receptor complex to activate JAK-STAT signaling. Reason: IL-10 signaling through JAK1/TYK2/STAT3 is a core pathway. This NAS annotation from ComplexPortal is consistent with the well-established signaling mechanism (deep research review). Supporting Evidence: PMID:33737461 We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. |
| GO:0008284 positive regulation of cell population proliferation | NAS PMID:31611251 Biology and therapeutic potential of interleukin-10. | KEEP AS NON CORE | Summary: NAS annotation for positive regulation of cell proliferation from PMID:31611251 (ComplexPortal). Reason: IL-10 can promote proliferation of certain cell types, particularly B cells and mast cells. However, it also inhibits proliferation of other cell types (T cells). This is a context-dependent effect, keep as non-core. Supporting Evidence: PMID:31611251 IL-10 (Fiorentino et al., 1989; Moore et al., 1990) is the founding member of a family of cytokines that also includes IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29 |
| GO:0019221 cytokine-mediated signaling pathway | NAS PMID:33737461 Structure-based decoupling of the pro- and anti-inflammatory... | ACCEPT | Summary: NAS annotation for cytokine-mediated signaling pathway from ComplexPortal. Reason: IL-10 is a cytokine that mediates signaling through its receptor. This is a core annotation that is well-supported (deep research review). Supporting Evidence: PMID:33737461 Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. |
| GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein | NAS PMID:16982608 Conformational changes mediate interleukin-10 receptor 2 (IL... | ACCEPT | Summary: NAS annotation for positive regulation of STAT tyrosine phosphorylation from PMID:16982608. Reason: IL-10 signaling leads to JAK1/TYK2-mediated tyrosine phosphorylation of STAT3, which is the canonical downstream signaling event. This is a core mechanistic annotation (PMID:16982608, deep research review). Supporting Evidence: PMID:16982608 The basic mechanistic features of the assembly process are likely shared by six additional class-2 cytokines (viral IL-10s, IL-22, IL-26, IL-28A, IL28B, and IL-29) to promote IL-10R2 binding to six additional receptor complexes. |
| GO:0050728 negative regulation of inflammatory response | NAS PMID:31611251 Biology and therapeutic potential of interleukin-10. | ACCEPT | Summary: NAS annotation for negative regulation of inflammatory response from ComplexPortal. Reason: Anti-inflammatory activity is the core function of IL-10. Multiple evidence codes support this annotation (IBA, IDA, NAS from multiple sources). Supporting Evidence: PMID:31611251 The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of a host from over-exuberant responses to pathogens and microbiota |
| GO:0050728 negative regulation of inflammatory response | NAS PMID:21857966 WNT5A signaling contributes to AΞ²-induced neuroinflammation ... | ACCEPT | Summary: NAS annotation for negative regulation of inflammatory response from PMID:21857966, which is about WNT5A signaling and neuroinflammation. Reason: While PMID:21857966 is primarily about WNT5A, IL-10 is mentioned as an anti-inflammatory cytokine in the context of neuroinflammation. The annotation itself is correct regardless of the reference context. Supporting Evidence: PMID:21857966 We found that IL-10, a prototypic anti-inflammatory cytokine, caused concentration-dependent rescue effects on AΞ² toxicity |
| GO:0034115 negative regulation of heterotypic cell-cell adhesion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation transferred from mouse Il10 (P18893) for negative regulation of heterotypic cell-cell adhesion. IL-10 downregulates adhesion molecules. Reason: IL-10 downregulates ICAM-1 and other adhesion molecules on monocytes (PMID:7512027 per UniProt), which affects cell-cell adhesion. Transfer from mouse Il10 is reasonable. Keep as non-core. |
| GO:0034116 positive regulation of heterotypic cell-cell adhesion | ISS GO_REF:0000024 | REMOVE | Summary: ISS annotation whose WITH/FROM in the GOA file is UniProtKB:P06804, which was verified against UniProt to be TNFA_MOUSE (mouse tumor necrosis factor), not an IL-10 orthologue. ISS requires a sequence-similarity basis, and mouse TNF is a compact beta-sandwich (jelly-roll) TNF-superfamily ligand with no detectable homology to the class-II four-helix-bundle IL-10 fold, so no sequence-similarity transfer between them is possible. The four ISS rows sourced from P06804 (GO:0034116, GO:0045930, GO:0072577, GO:1904707) sit alongside four ISS rows correctly sourced from mouse Il10 (P18893, GO:0034115, GO:1904706, GO:0008285, GO:1903034), and in two cases the P06804-derived term is the exact opposite of the P18893-derived one (GO:0034116 vs GO:0034115; GO:1904707 vs GO:1904706). That pattern is the signature of a wrong accession having been entered for these rows, and the terms themselves are classic TNF activities. Reason: Upregulation of endothelial adhesion molecules to promote heterotypic leukocyte adhesion is a canonical TNF activity, and it is the direct opposite of the effect of IL-10, which downregulates ICAM-1 and other adhesion molecules and is separately annotated to GO:0034115 (negative regulation of heterotypic cell-cell adhesion) by ISS from the genuine mouse Il10 orthologue. Since ISS requires sequence similarity and P06804 (mouse TNF) is not homologous to IL-10, this annotation has no valid inferential basis and contradicts IL-10 biology. Remove. |
| GO:0045930 negative regulation of mitotic cell cycle | ISS GO_REF:0000024 | REMOVE | Summary: ISS annotation whose WITH/FROM is UniProtKB:P06804, verified against UniProt to be TNFA_MOUSE (mouse tumor necrosis factor), not an IL-10 orthologue. One of the four P06804-sourced ISS rows discussed under GO:0034116. Reason: ISS requires a sequence-similarity basis, and mouse TNF (a TNF-superfamily beta-sandwich ligand) shares no homology with the four-helix-bundle IL-10 fold, so nothing can legitimately be transferred from it to IL10. TNF-induced cell cycle arrest operates through TNFR1/TNFR2 death-domain and NF-kB signalling with no mechanistic parallel in IL-10 / IL-10R / STAT3 signalling, and IL-10's documented anti-proliferative effects are separately and properly captured by GO:0008285 (ISS from mouse Il10, P18893) and GO:0042130. Remove. |
| GO:0072577 endothelial cell apoptotic process | ISS GO_REF:0000024 | REMOVE | Summary: ISS annotation whose WITH/FROM is UniProtKB:P06804, verified against UniProt to be TNFA_MOUSE (mouse tumor necrosis factor), not an IL-10 orthologue. One of the four P06804-sourced ISS rows discussed under GO:0034116. Reason: ISS requires sequence similarity, and mouse TNF is not homologous to IL-10, so the transfer has no valid basis. Beyond that, the direction is wrong for IL-10 - TNF is a canonical inducer of endothelial apoptosis, whereas IL-10 is protective toward endothelium and carries its own IMP annotation to GO:2000352 (negative regulation of endothelial cell apoptotic process; PMID:16034134). Retaining the unqualified parent process term here would imply IL-10 participates in killing endothelial cells. Remove. |
| GO:1904706 negative regulation of vascular associated smooth muscle cell proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation transferred from mouse Il10 (P18893). IL-10 may inhibit vascular smooth muscle cell proliferation. Reason: Transfer from mouse Il10 (P18893) is reasonable in principle, but regulation of vascular smooth muscle cell proliferation is a peripheral non-immune effect. Over-annotation for this immune cytokine. |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | ISS GO_REF:0000024 | REMOVE | Summary: ISS annotation whose WITH/FROM is UniProtKB:P06804, verified against UniProt to be TNFA_MOUSE (mouse tumor necrosis factor), not an IL-10 orthologue. One of the four P06804-sourced ISS rows discussed under GO:0034116, and the direct opposite of GO:1904706, which IL10 receives by ISS from the genuine mouse Il10 orthologue P18893. Reason: ISS requires sequence similarity, and mouse TNF is not homologous to IL-10, so no transfer is possible. Promotion of vascular smooth muscle cell proliferation is a TNF activity; the co-occurrence of this term with the opposite term GO:1904706 sourced from mouse Il10 in the same GO_REF:0000024 batch confirms that P06804 is a wrong-accession artifact rather than a considered assertion about IL-10. Remove. |
| GO:0008285 negative regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation transferred from mouse Il10 (P18893). IL-10 can inhibit proliferation of certain cell types. Reason: IL-10 can inhibit T cell proliferation (PMID:8499633) and has anti-proliferative effects on certain cell types. Transfer from mouse Il10 is reasonable. Keep as non-core. |
| GO:1903034 regulation of response to wounding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation transferred from mouse Il10 (P18893). IL-10 modulates wound healing through anti-inflammatory effects. Reason: IL-10 modulates wound healing responses through its anti-inflammatory properties. Transfer from mouse Il10 is reasonable. Keep as non-core. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-449803 | ACCEPT | Summary: TAS annotation for extracellular region from Reactome (IL10 dimer binds IL10RA:JAK1). IL-10 is a secreted protein. Reason: IL-10 is secreted and localizes to the extracellular region where it binds its receptor complex. Reactome pathway annotation is consistent with known biology. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-449811 | ACCEPT | Summary: TAS for extracellular region from Reactome (IL10 dimer:2xIL10RA1:JAK1 binds IL10RB:TYK2). Reason: Same as above. IL-10 is extracellular. Reactome annotation consistent with known biology. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-449855 | ACCEPT | Summary: TAS for extracellular region from Reactome (IL10 dimerizes). Reason: IL-10 dimerizes in the extracellular space. Correct annotation. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784006 | ACCEPT | Summary: TAS for extracellular region from Reactome (STAT3 phosphorylation by JAK1/TYK2). Reason: IL-10 is the extracellular ligand in this signaling event. Correct. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784319 | ACCEPT | Summary: TAS for extracellular region from Reactome (JAK1,TYK2 phosphorylation). Reason: IL-10 is extracellular during this signaling step. Correct. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784323 | ACCEPT | Summary: TAS for extracellular region from Reactome (receptor complex binds STAT3). Reason: IL-10 remains in the extracellular region bound to its receptor. Correct. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784324 | ACCEPT | Summary: TAS for extracellular region from Reactome (IL10RA phosphorylation). Reason: IL-10 is extracellular in this signaling context. Correct. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784791 | ACCEPT | Summary: TAS for extracellular region from Reactome (STAT3 dissociation from receptor). Reason: IL-10 is extracellular. Correct. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6789615 | ACCEPT | Summary: TAS for extracellular region from Reactome (STAT3-upregulated extracellular protein expression). Reason: IL-10 is extracellular. Correct. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8981073 | ACCEPT | Summary: TAS for extracellular region from Reactome (Expression of Interleukin-10). Reason: IL-10 is expressed and secreted to the extracellular region. Correct. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9664346 | ACCEPT | Summary: TAS for extracellular region from Reactome (IL10 gene produces IL10 protein). Reason: IL-10 is a secreted extracellular protein. Correct. |
| GO:0005615 extracellular space | IDA PMID:21323571 Pro/anti-inflammatory cytokines in the pathogenesis of prema... | ACCEPT | Summary: IDA for extracellular space from PMID:21323571, which studied cytokines in premature coronary artery disease patients. Reason: IL-10 is detected in the extracellular space (serum/plasma) of patients. Consistent with IL-10 being a secreted cytokine. Supporting Evidence: PMID:21323571 Serum IL-10, IL-18, and TNF-alpha were measured using enzyme-linked immunosorbent assay |
| GO:0032692 negative regulation of interleukin-1 production | TAS PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patche... | ACCEPT | Summary: TAS annotation for negative regulation of IL-1 production from PMID:19262501, about regulatory B cells in sheep Peyer's patches that secrete IL-10 and downregulate TLR9-induced cytokine responses. Reason: IL-10 inhibition of IL-1 production is well-established as part of its core anti-inflammatory function. The original CSIF description (PMID:1940799) showed IL-10 inhibits multiple pro-inflammatory cytokines. PMID:19262501 provides additional evidence from Peyer's patch B cells. Supporting Evidence: PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patches spontaneously secretes IL-10 and downregulates TLR9-induced IFNalpha responses. |
| GO:0032695 negative regulation of interleukin-12 production | TAS PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patche... | ACCEPT | Summary: TAS for negative regulation of IL-12 production from PMID:19262501. Reason: IL-10 inhibition of IL-12 production by monocytes/macrophages and dendritic cells is one of its most important anti-inflammatory activities. IL-12 suppression is critical for limiting Th1 responses (PMID:19262501, deep research review). Supporting Evidence: PMID:19262501 Neutralization of the IL-10 or depletion of CD21(+) B cells resulted in a significant increase in CpG-induced IFNalpha-response in PPs, suggesting that IL-10 from B cells regulate innate responses in PPs. |
| GO:0032701 negative regulation of interleukin-18 production | TAS PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patche... | ACCEPT | Summary: TAS for negative regulation of IL-18 production from PMID:19262501. Reason: IL-10 suppression of IL-18 production is consistent with its broad anti-inflammatory activity. IL-18 is a pro-inflammatory cytokine that IL-10 is known to suppress (PMID:19262501). Supporting Evidence: PMID:19262501 PP cells spontaneously secreted high levels of IL-10, and the primary source of the IL-10 was resting CD5(-)CD11c(-)CD21(+) B cells. |
| GO:0032715 negative regulation of interleukin-6 production | TAS PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patche... | ACCEPT | Summary: TAS for negative regulation of IL-6 production from PMID:19262501. Reason: IL-10 inhibition of IL-6 production is well-established and also supported by IDA annotation from PMID:10443688 (PMID:19262501). Supporting Evidence: PMID:19262501 PP cells spontaneously secreted high levels of IL-10, and the primary source of the IL-10 was resting CD5(-)CD11c(-)CD21(+) B cells. |
| GO:0032717 negative regulation of interleukin-8 production | TAS PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patche... | ACCEPT | Summary: TAS for negative regulation of IL-8 production from PMID:19262501. Reason: IL-10 inhibition of IL-8 (CXCL8) production is part of its broad suppression of pro-inflammatory mediators (PMID:19262501). Supporting Evidence: PMID:19262501 PP cells spontaneously secreted high levels of IL-10, and the primary source of the IL-10 was resting CD5(-)CD11c(-)CD21(+) B cells. |
| GO:0032720 negative regulation of tumor necrosis factor production | TAS PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patche... | ACCEPT | Summary: TAS for negative regulation of TNF production from PMID:19262501. Reason: IL-10 suppression of TNF production is one of the earliest and best characterized functions of IL-10 (PMID:1940799, PMID:19262501). Supporting Evidence: PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patches spontaneously secretes IL-10 and downregulates TLR9-induced IFNalpha responses. |
| GO:0071650 negative regulation of chemokine (C-C motif) ligand 5 production | TAS PMID:19262501 A novel regulatory B-cell population in sheep Peyer's patche... | ACCEPT | Summary: TAS for negative regulation of CCL5 (RANTES) production from PMID:19262501. Reason: IL-10 suppression of chemokine production including CCL5/RANTES is consistent with its broad anti-inflammatory activity (PMID:19262501). Supporting Evidence: PMID:19262501 These IL-10-secreting PP B cells may represent a novel subset of the recently proposed regulatory B cells (B(regs)) in the intestine. |
| GO:1903659 regulation of complement-dependent cytotoxicity | IMP NOT PMID:16034134 IL-4 and IL-13 induce protection of porcine endothelial cell... | ACCEPT | Summary: NOT annotation: IL-10 does NOT regulate complement-dependent cytotoxicity based on PMID:16034134. Reason: This is a NOT annotation indicating IL-10 was tested and found not to regulate complement-dependent cytotoxicity. Negative results are informative and should be retained. Supporting Evidence: PMID:16034134 porcine EC incubated with IL-4 or IL-13, but not with IL-10 or IL-11, became protected from killing by complement and apoptosis induced by TNF-alpha plus cycloheximide. |
| GO:2000352 negative regulation of endothelial cell apoptotic process | IMP NOT PMID:16034134 IL-4 and IL-13 induce protection of porcine endothelial cell... | ACCEPT | Summary: NOT annotation: IL-10 does NOT negatively regulate endothelial cell apoptotic process based on PMID:16034134. Reason: This is a NOT annotation indicating IL-10 was tested and found not to inhibit endothelial cell apoptosis. Negative results are informative. Supporting Evidence: PMID:16034134 porcine EC incubated with IL-4 or IL-13, but not with IL-10 or IL-11, became protected from killing by complement and apoptosis induced by TNF-alpha plus cycloheximide. |
| GO:0042130 negative regulation of T cell proliferation | NAS PMID:14971032 Interleukin 10 regulates cell surface and soluble LIR-2 (CD8... | ACCEPT | Summary: NAS for negative regulation of T cell proliferation from PMID:14971032. IL-10 upregulates LIR-2 on DCs, causing T cell hyporesponsiveness. Reason: IL-10 inhibition of T cell proliferation is well-documented. PMID:14971032 showed IL-10 regulates LIR-2 on dendritic cells resulting in T cell hyporesponsiveness. Also supported by PMID:8499633 which showed direct inhibition of T cell growth. Supporting Evidence: PMID:14971032 Interleukin 10 regulates cell surface and soluble LIR-2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro. PMID:8499633 Human interleukin-10 (IL-10) inhibits T-cell proliferation and cytokine production in the presence of monocytes. |
| GO:0071222 cellular response to lipopolysaccharide | NAS PMID:14971032 Interleukin 10 regulates cell surface and soluble LIR-2 (CD8... | KEEP AS NON CORE | Summary: NAS for cellular response to LPS from PMID:14971032. IL-10 modulates the response to LPS. Reason: IL-10 modulates the cellular response to LPS stimulation by suppressing pro-inflammatory cytokine production. This is a stimulus-response context for IL-10 function. Keep as non-core. Supporting Evidence: PMID:14971032 LPS-stimulated, LIR-2-transfected DC inhibited the proliferation of T cells in autologous, as well as allogeneic culture systems in vitro. |
| GO:0060302 negative regulation of cytokine activity | IMP PMID:9847016 Human interleukin 10 suppresses production of inflammatory m... | ACCEPT | Summary: IMP annotation for negative regulation of cytokine activity from PMID:9847016. IL-10 suppresses cytokine activity as part of its anti-inflammatory program. Reason: IL-10 negatively regulates the activity of multiple pro-inflammatory cytokines. This is consistent with its core anti-inflammatory function. Supporting Evidence: PMID:9847016 Preincubation of LPS-stimulated peritoneal macrophages with rhuIL-10 caused significant (P<0.05) reduction in secretion of TNF, IL-6, and PGE2, in a dose-dependent manner. |
| GO:0002904 positive regulation of B cell apoptotic process | IDA PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by ... | KEEP AS NON CORE | Summary: IDA for positive regulation of B cell apoptotic process from PMID:9184696. This paper showed dual effects of IL-10 on SAC-activated B cells: promoting apoptosis at the initiation of activation and proliferation after pre-activation. Reason: PMID:9184696 demonstrated that IL-10 has dual effects on B cells depending on activation state. IL-10 induces apoptosis in B cells at early stages of activation while promoting survival/proliferation of pre-activated B cells. The pro-apoptotic effect is context-dependent and not a core function. Supporting Evidence: PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by IL-10 are associated with changes in Bcl-2, Bcl-xL, and Mcl-1 expression. |
| GO:0010468 regulation of gene expression | IDA PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by ... | KEEP AS NON CORE | Summary: IDA for regulation of gene expression from PMID:9184696. IL-10 treatment altered expression of Bcl-2, Bcl-xL, and Mcl-1 in B cells. Reason: IL-10 does regulate gene expression through STAT3 signaling. This is a very broad term; the specific gene expression changes (Bcl-2 family members) are context-specific to the B cell activation study (PMID:9184696). Keep as non-core. Supporting Evidence: PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by IL-10 are associated with changes in Bcl-2, Bcl-xL, and Mcl-1 expression. |
| GO:0030889 negative regulation of B cell proliferation | IDA PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by ... | KEEP AS NON CORE | Summary: IDA for negative regulation of B cell proliferation from PMID:9184696. Context-dependent effect of IL-10 on B cell proliferation. Reason: PMID:9184696 showed that IL-10 can inhibit B cell proliferation depending on the activation state of the B cells. This is a real but context-dependent effect. Keep as non-core. Supporting Evidence: PMID:9184696 The apoptosis and proliferation of SAC-activated B cells by IL-10 are associated with changes in Bcl-2, Bcl-xL, and Mcl-1 expression. |
| GO:0051045 negative regulation of membrane protein ectodomain proteolysis | IDA PMID:18383040 Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/A... | KEEP AS NON CORE | Summary: IDA for negative regulation of membrane protein ectodomain proteolysis from PMID:18383040. IL-10 may inhibit shedding of certain membrane proteins. Reason: PMID:18383040 showed IL-10 inhibits TACE/ADAM-17 activity on monocytes, which regulates TNF-alpha shedding. This is a downstream effect of IL-10 anti-inflammatory signaling. Keep as non-core. Supporting Evidence: PMID:18383040 In the presence of IL-10, TNF-alpha production and activation of surface TACE was significantly inhibited. |
| GO:0001819 positive regulation of cytokine production | IDA PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | KEEP AS NON CORE | Summary: IDA for positive regulation of cytokine production from PMID:10443688. IL-10 can positively regulate production of certain cytokines while suppressing others. Reason: While IL-10 is primarily known as an inhibitor of pro-inflammatory cytokines, it can promote production of certain cytokines (e.g., it can enhance IL-1RA production). This dual activity is consistent with IL-10 biology. Keep as non-core since the primary function is anti-inflammatory. Supporting Evidence: PMID:10443688 its effect on IL-10 secretion was biphasic, producing stimulation at lower, and inhibition at higher doses. |
| GO:0002719 negative regulation of cytokine production involved in immune response | IDA PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | ACCEPT | Summary: IDA for negative regulation of cytokine production in immune response from PMID:10443688. Reason: This is a core function of IL-10. It specifically captures the immune context of IL-10's cytokine-suppressive activity. More specific than the general negative regulation of cytokine production (GO:0001818) and directly relevant to IL-10's primary role. Supporting Evidence: PMID:10443688 Dexamethasone had different effects on LPS-induced TNFalpha and IL-10 secretion; whereas it suppressed TNFalpha in a dose-dependent fashion |
| GO:0005125 cytokine activity | NAS PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | ACCEPT | Summary: NAS for cytokine activity from PMID:10443688. Redundant with IBA and IDA annotations. Reason: Cytokine activity is the core molecular function. Multiple evidence codes support this annotation. Supporting Evidence: PMID:10443688 interleukin (IL)-10 (an anti-inflammatory cytokine) |
| GO:0005615 extracellular space | IDA PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | ACCEPT | Summary: IDA for extracellular space from PMID:10443688. Reason: IL-10 is secreted and found in the extracellular space. Well-established. Supporting Evidence: PMID:10443688 the sensitivity of these cells to glucocorticoids is altered by TNFalpha or IL-10 pretreatment |
| GO:0032715 negative regulation of interleukin-6 production | IDA PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | ACCEPT | Summary: IDA for negative regulation of IL-6 production from PMID:10443688. Reason: IL-10 suppression of IL-6 production is a well-characterized core anti-inflammatory activity. Also supported by TAS from PMID:19262501. Supporting Evidence: PMID:10443688 with IL-10 improved, the ability of dexamethasone to suppress IL-6 secretion in whole-blood cell cultures |
| GO:0051384 response to glucocorticoid | IDA PMID:10443688 Tumor necrosis factor alpha decreases, and interleukin-10 in... | KEEP AS NON CORE | Summary: IDA for response to glucocorticoid from PMID:10443688. IL-10 expression is regulated by glucocorticoids. Reason: Glucocorticoid regulation of IL-10 expression is documented but describes regulation of IL-10 rather than a core function of IL-10 itself. Keep as non-core. Supporting Evidence: PMID:10443688 IL-10 increased (P < 0.001), the concentration of dexamethasone binding sites in these cells |
| GO:0002237 response to molecule of bacterial origin | IDA PMID:17449476 Eis (enhanced intracellular survival) protein of Mycobacteri... | KEEP AS NON CORE | Summary: IDA for response to molecule of bacterial origin from PMID:17449476. IL-10 is produced in response to bacterial products. Reason: IL-10 production is induced by bacterial products as part of the immune response regulatory feedback loop. This describes a context for IL-10 induction rather than a core function. Keep as non-core. Supporting Evidence: PMID:17449476 there is increased production of interferon-gamma and interleukin-10, which indicates that immunity in response to Eis treatment is skewed away from a protective T(H)1 response |
| GO:0030595 leukocyte chemotaxis | TAS PMID:9405662 Identification of functional domains on human interleukin 10 | KEEP AS NON CORE | Summary: TAS for leukocyte chemotaxis from PMID:9405662. This paper identified functional domains on human IL-10 (also referenced for protein sequence in UniProt). Reason: IL-10 can modulate leukocyte chemotaxis through its effects on chemokine production and adhesion molecule expression. PMID:9405662 studied functional domains of IL-10 including chemotactic effects. Keep as non-core. Supporting Evidence: PMID:9405662 IL-10 significantly affects chemokine biology, because human IL-10 inhibits chemokine production and is a specific chemotactic factor for CD8+ T cells. |
| GO:0030183 B cell differentiation | NAS PMID:8228801 Interleukin 10 (IL-10) upregulates functional high affinity ... | KEEP AS NON CORE | Summary: NAS for B cell differentiation from PMID:8228801. IL-10 promotes B cell differentiation. Reason: IL-10 promotes B cell differentiation, particularly plasma cell differentiation. This is a well-established but non-core function of IL-10 (PMID:8228801, PMID:9184696). Supporting Evidence: PMID:8228801 Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. |
| GO:0042100 B cell proliferation | NAS PMID:8228801 Interleukin 10 (IL-10) upregulates functional high affinity ... | KEEP AS NON CORE | Summary: NAS for B cell proliferation from PMID:8228801. IL-10 promotes B cell proliferation in certain contexts. Reason: IL-10 was originally identified as a B cell growth factor as well as a cytokine synthesis inhibitor. It promotes B cell proliferation of pre-activated B cells (PMID:8228801, PMID:9184696). Keep as non-core. Supporting Evidence: PMID:8228801 IL-2 and IL-10 were found to synergize to induce the proliferation and differentiation of B-CLL cells. |
| GO:0045191 regulation of isotype switching | NAS PMID:8228801 Interleukin 10 (IL-10) upregulates functional high affinity ... | KEEP AS NON CORE | Summary: NAS for regulation of isotype switching from PMID:8228801. IL-10 regulates immunoglobulin isotype switching in B cells. Reason: IL-10 is known to regulate immunoglobulin isotype switching, promoting certain isotype classes. This is a real but non-core function related to IL-10's effects on B cells (PMID:8228801). Supporting Evidence: PMID:8228801 normal B cells which proliferated strongly and secreted large amounts of IgM, IgG, and IgA. |
| GO:0005141 interleukin-10 receptor binding | NAS PMID:1847510 Isolation and expression of human cytokine synthesis inhibit... | ACCEPT | Summary: NAS for IL-10 receptor binding from PMID:1847510. This is the seminal paper on IL-10 cDNA cloning (Vieira et al., 1991). Reason: IL-10 receptor binding is a core molecular function. PMID:1847510 is the original cloning paper for human IL-10 (Vieira et al., PNAS 1991) and established IL-10 as a ligand for its receptor. Supporting Evidence: PMID:1847510 cDNA clones encoding human IL-10 (hIL-10) were isolated from a tetanus toxin-specific human T-cell clone. |
| GO:0008083 growth factor activity | NAS PMID:1371884 Interleukin 10 is a potent growth and differentiation factor... | MODIFY | Summary: NAS for growth factor activity from PMID:1371884. IL-10 was early on characterized as having growth factor-like activity on B cells. Reason: While IL-10 does have proliferation-promoting effects on certain cell types (B cells, mast cells), it is more accurately classified as a cytokine than a growth factor. The term "cytokine activity" (GO:0005125) is more appropriate. Growth factor activity implies a more general proliferative function that does not capture IL-10's primary immunomodulatory role. Proposed replacements: cytokine activity Supporting Evidence: PMID:1371884 human and viral IL-10 stimulate DNA replication of B lymphocytes activated either via their antigen receptor or via their CD40 antigen. |
| GO:0030097 hemopoiesis | TAS PMID:11244051 Interleukin-10 and the interleukin-10 receptor. | KEEP AS NON CORE | Summary: TAS for hemopoiesis from PMID:11244051. IL-10 has effects on hematopoietic cell development. Reason: IL-10 has effects on hematopoietic cell development and differentiation, particularly on monocyte/macrophage and B cell lineages. This is a broad term but represents a real function. Keep as non-core. Supporting Evidence: PMID:11244051 multifunctional cytokine with diverse effects on most hemopoietic cell types. |
| GO:0032687 negative regulation of interferon-alpha production | NAS PMID:9637497 Exogenous and endogenous IL-10 regulate IFN-alpha production... | ACCEPT | Summary: NAS for negative regulation of IFN-alpha production from PMID:9637497. This paper demonstrated that IL-10 reduces IFN-alpha-producing cells and bulk IFN-alpha in response to viral stimulation. Reason: PMID:9637497 directly demonstrated that IL-10 suppresses IFN-alpha production by PBMCs in response to multiple viruses (HSV-1, Sendai virus, NDV, VSV). This is a specific and well-documented anti-inflammatory function of IL-10. Supporting Evidence: PMID:9637497 Human IL-10 (hIL-10) caused reductions in both the frequency of IFN-alpha-producing cells (IPC) and bulk IFN in response to herpes simplex virus type-1 (HSV-1), Sendai virus, Newcastle disease virus, and vesicular stomatitis virus. |
| GO:0042092 type 2 immune response | TAS PMID:11244051 Interleukin-10 and the interleukin-10 receptor. | KEEP AS NON CORE | Summary: TAS for type 2 immune response from PMID:11244051. IL-10 is associated with Th2/type 2 immune responses. Reason: IL-10 was originally identified as a Th2-derived cytokine and is associated with type 2 immune responses. However, IL-10 is now known to be produced by diverse immune cell types, not exclusively Th2 cells. The association with type 2 immunity is a non-core aspect of IL-10 biology. Supporting Evidence: PMID:11244051 IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. |
| GO:0042130 negative regulation of T cell proliferation | NAS PMID:8499633 Human interleukin-10 can directly inhibit T-cell growth | ACCEPT | Summary: NAS for negative regulation of T cell proliferation from PMID:8499633, which directly demonstrated that IL-10 inhibits T cell growth. Reason: PMID:8499633 showed that IL-10 directly inhibits T cell growth (55.4% inhibition) when stimulated with immobilized anti-CD3, even in the absence of monocytes. This establishes a direct effect on T cells. Supporting Evidence: PMID:8499633 highly purified peripheral blood T cells containing less than 0.1% CD14+ cells and unresponsive to phytohemagglutinin (PHA), were growth-inhibited by IL-10 when stimulated with immobilized OKT3 monoclonal antibody (MoAb; 55.4% inhibition). |
| GO:0043066 negative regulation of apoptotic process | NAS PMID:8312229 IL-10 inhibits apoptotic cell death in human T cells starved... | KEEP AS NON CORE | Summary: NAS for negative regulation of apoptotic process from PMID:8312229, which showed IL-10 inhibits apoptotic cell death in T cells starved of IL-2. Reason: PMID:8312229 demonstrated that IL-10 inhibits apoptosis in IL-2-deprived T cells. This is a real but context-dependent anti-apoptotic effect of IL-10. Keep as non-core. Supporting Evidence: PMID:8312229 IL-10 inhibits apoptotic cell death in human T cells starved of IL-2. |
| GO:0045347 negative regulation of MHC class II biosynthetic process | TAS PMID:11244051 Interleukin-10 and the interleukin-10 receptor. | ACCEPT | Summary: TAS for negative regulation of MHC class II biosynthesis from PMID:11244051. Reason: IL-10 downregulation of MHC class II expression is a core function, also supported by IDA from PMID:1940799 (PMID:11244051, PMID:1940799). Supporting Evidence: PMID:11244051 IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. |
| GO:0005576 extracellular region | IPI PMID:33737461 Structure-based decoupling of the pro- and anti-inflammatory... | ACCEPT | Summary: IPI for extracellular region from PMID:33737461 (ComplexPortal). Reason: IL-10 is a secreted protein found in the extracellular region. Correct. Supporting Evidence: PMID:33737461 We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. |
| GO:0045063 T-helper 1 cell differentiation | IDA PMID:33737461 Structure-based decoupling of the pro- and anti-inflammatory... | KEEP AS NON CORE | Summary: IDA for T-helper 1 cell differentiation from PMID:33737461 (ComplexPortal). IL-10 can influence Th1/Th2 balance. Reason: IL-10 can influence T helper cell differentiation, particularly by suppressing Th1 differentiation through inhibition of IL-12 and IFN-gamma production. The annotation says Th1 differentiation, not inhibition of it, so the qualifier from the GOA should be checked. Keep as non-core. Supporting Evidence: PMID:33737461 Some variants displayed myeloid-biased activity by suppressing macrophage activation without stimulating inflammatory CD8+ T cells, thereby uncoupling the major opposing functions of IL-10. |
| GO:0002639 positive regulation of immunoglobulin production | IGI PMID:22962438 Complement receptor type 1 (CR1, CD35) is a potent inhibitor... | KEEP AS NON CORE | Summary: IGI for positive regulation of immunoglobulin production from PMID:22962438, with genetic interaction with IL-6 (P60568). Reason: IL-10 promotes immunoglobulin production by B cells, often in synergy with other cytokines like IL-6. This is consistent with IL-10's B cell-stimulatory functions. Keep as non-core. Supporting Evidence: PMID:22962438 CR1 inhibits the differentiation of B cells to plasmablasts and their immunoglobulin production. |
| GO:1900100 positive regulation of plasma cell differentiation | IGI PMID:22962438 Complement receptor type 1 (CR1, CD35) is a potent inhibitor... | KEEP AS NON CORE | Summary: IGI for positive regulation of plasma cell differentiation from PMID:22962438, with genetic interaction with IL-6 (P60568). Reason: IL-10 promotes plasma cell differentiation, consistent with its B cell stimulatory functions. Keep as non-core. Supporting Evidence: PMID:22962438 CR1 inhibits the differentiation of B cells to plasmablasts and their immunoglobulin production. |
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