Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
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Many IEA transfers from rat Il10 (P29456) represent peripheral observations (response to xenobiotic, activity, inactivity, carbon monoxide, insulin, estradiol) that are over-annotations for human IL-10 core function.
Combined Automated Annotation using Multiple IEA Methods
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IEA annotations for core functions (cytokine activity, extracellular space, immune response, TNF regulation) are correct.
Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.
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Seminal paper establishing IL-10 as a cytokine synthesis inhibitor.
"IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level."
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Demonstrated inhibition of cytokine production and MHC class II expression.
"IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level."
Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells
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This paper is about OX40L (TNFSF4), NOT about IL-10. Two IDA annotations cite this paper for IL-10, which appears to be a reference error.
"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."
IL-10 inhibits apoptotic cell death in human T cells starved of IL-2
Human interleukin-10 can directly inhibit T-cell growth
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IL-10 directly inhibits T cell growth (55.4% inhibition with anti-CD3).
"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)."
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Effect is independent of monocytes.
"Thus, IL-10 can directly inhibit growth and IL-2 production in T cells triggered by immobilized OKT3 MoAb in the absence of monocytes."
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
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IL-10 has dual effects on B cells depending on activation state -- apoptosis at initiation versus proliferation after pre-activation.
"the addition of IL-10 at the initiation of activation down-regulated Bcl-xL, Bcl-2, and Mcl-1 expression. At the same time, B cell proliferation was inhibited and apoptotic cell number increased, suggesting the growth arrest and/or apoptosis of B cells."
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In contrast, IL-10 supported proliferation and differentiation of pre-activated B cells.
"In contrast, IL-10 failed to down-regulate the Bcl-xL and Bcl-2 expression but rather augmented the expression of Mcl-1 of B cells after preactivation for 48 hr with SAC and IL-2"
Exogenous and endogenous IL-10 regulate IFN-alpha production by peripheral blood mononuclear cells in response to viral stimulation
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IL-10 reduces frequency of IFN-alpha-producing cells and bulk IFN-alpha.
"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."
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Effect seen with HSV-1, Sendai virus, NDV, and VSV stimulation.
"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."
Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone; potential regulation of the glucocorticoid receptor.
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IL-10 increases the sensitivity of human monocytes to dexamethasone and enhances glucocorticoid receptor concentration, supporting IL-10 anti-inflammatory synergy with glucocorticoids.
"Pretreatment with TNFalpha diminished, and with IL-10 improved, the ability of dexamethasone to suppress IL-6 secretion in whole-blood cell cultures (P < 0.01 for both) and to enhance IL-1 receptor antagonist secretion by U937 cells (P < 0.05 for both)."
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IL-10 increased the concentration of dexamethasone binding sites (glucocorticoid receptor) in monocytes.
"TNFalpha decreased (P < 0.001), while IL-10 increased (P < 0.001), the concentration of dexamethasone binding sites in these cells, with no discernible effect on their binding affinity."
Interleukin 10 regulates cell surface and soluble LIR-2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro
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IL-10 upregulates LIR-2 on DCs.
"the inhibitory receptor LIR-2 (leukocyte immunoglobulin-like receptor-2, CD85d) is specifically up-regulated by IL-10 on maturing human DC"
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Results in T cell hyporesponsiveness.
"IL-10 renders DC hypostimulatory by up-regulating cell surface LIR-2 and by inhibiting soluble LIR-2 in vitro"
Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex.
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Key reference for IL-10 receptor interaction and JAK-STAT signaling.
"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"
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Used for protein dimerization, receptor binding, and signaling annotations.
"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."
A novel regulatory B-cell population in sheep Peyer's patches spontaneously secretes IL-10 and downregulates TLR9-induced IFNalpha responses
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B cells secrete IL-10 that suppresses multiple pro-inflammatory cytokines.
"PP cells spontaneously secreted high levels of IL-10, and the primary source of the IL-10 was resting CD5(-)CD11c(-)CD21(+) B cells."
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Supports TAS annotations for specific cytokine suppression.
"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."
IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways
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IL-10 inhibits autophagy via STAT3/AKT-mTOR crosstalk.
"IL10 inhibited starvation-induced autophagy and induced the expression of p-AKT and p-STAT3 in HSFs in a dose-dependent manner."
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Context-specific effect in hypertrophic scar fibroblasts.
"IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways."
A reference map of the human binary protein interactome
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HuRI high-throughput Y2H screen.
"With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies."
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Interactions with keratins and other non-immune proteins are likely false positives for a secreted cytokine.
"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."
Interleukin-10 conjugated electrospun polycaprolactone (PCL) nanofibre scaffolds for promoting alternatively activated (M2) macrophages around the peripheral nerve in vivo.
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Source of the rat Il10 IDA annotation to GO:0043032 that was electronically transferred to human IL10; IL-10 drives macrophages to the alternatively activated (M2) state in vivo.
"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."
Interleukin-10 and the interleukin-10 receptor.
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Referenced for hemopoiesis, type 2 immune response, and MHC class II regulation annotations.
"Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types."
Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI.
Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes.
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B cell differentiation, proliferation, and isotype switching regulation by IL-10.
"Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells."
Identification of functional domains on human interleukin 10
IL10 dimer binds IL10RA:JAK1
IL10 dimer:2xIL10RA1:JAK1 binds IL10RB:TYK2
STAT3 is phosphorylated by p-Y-JAK1,P-Y-TYK2
JAK1,TYK2 phosphorylate JAK1,TYK2
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3
p-Y-JAK1,p-Y-TYK2 phosphorylate IL10RA
p-Y705-STAT3 dissociates from IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2:p-Y705-STAT3
Expression of STAT3-upregulated extracellular proteins
Expression of Interleukin-10
IL10 gene produces IL10 protein
Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site.
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Structural basis of IL-10 binding to IL-10R1 (IL-10RA).
"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)."
Comparison of interleukin-22 and interleukin-10 soluble receptor complexes.
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Compares IL-22 and IL-10 receptor complex formation.
"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."
Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain.
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Crystal structure of EBV IL-10 bound to IL-10R1, informing human IL-10/receptor interaction.
"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."
Structure and mechanism of receptor sharing by the IL-10R2 common chain.
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Structural basis for IL-10R2 (IL-10RB) sharing among IL-10 family cytokines.
"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."
Human IL-10-producing B cells have diverse states that are induced from multiple B cell subsets.
Low IL10 serum levels as key factor for predicting the sustained virological response to IFNα/ribavirin in Brazilian patients with HCV carrying IL28B CT/TT genotype.
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Measures IL-10 serum levels in HCV patients, confirming IL-10 as a circulating cytokine.
"the levels of IL10 seem to influence response to IFNα/RIB therapy"
IL-10-induced microRNA-187 negatively regulates TNF-α, IL-6, and IL-12p40 production in TLR4-stimulated monocytes.
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IL-10 induces miR-187 which suppresses pro-inflammatory cytokine production.
"we identify miR-187 as an IL-10-dependent miRNA playing a role in IL-10-mediated suppression of TNF-α, IL-6, and the p40 subunit of IL-12"
B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma.
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IL-6 and IL-10 in the tumor microenvironment stimulate macrophage B7-H4 expression, contributing to immunosuppression.
"Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression."
Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma.
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Treg cells enable macrophages to produce IL-10 and IL-6, which in turn stimulate B7-H4 expression on macrophages in an autocrine manner.
"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."
Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10.
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Decouples IL-10 pro- and anti-inflammatory functions through structural analysis.
"IL-10 variants with a range of IL-10Rβ binding strengths uncovered substantial differences in response thresholds across immune cell populations, providing a means of manipulating IL-10 cell type selectivity."
Biology and therapeutic potential of interleukin-10.
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Comprehensive review of IL-10 biology and therapeutic applications.
"The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of a host from over-exuberant responses to pathogens and microbiota, while playing important roles in other settings as sterile wound healing, autoimmunity, cancer, and homeostasis."
WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity.
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IL-10 referenced as anti-inflammatory cytokine in neuroinflammation context.
"activation of Wnt5a signaling elicited the expression of proinflammatory cytokines IL-1β and TNF-α whereas inhibition of Wnt5a signaling attenuated the Aβ-induced expression of the cytokines in cortical cultures."
Pro/anti-inflammatory cytokines in the pathogenesis of premature coronary artery disease.
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IL-10 measured as anti-inflammatory cytokine in coronary artery disease.
"Proinflammatory interleukin-18 (IL-18), high-sensitivity C-reactive protein (hS-CRP), tumor necrosis factor-alpha (TNF-alpha), and anti-inflammatory IL-10 are involved in the pathogenesis of atherosclerosis."
IL-4 and IL-13 induce protection of porcine endothelial cells from killing by human complement and from apoptosis through activation of a phosphatidylinositide 3-kinase/Akt pathway.
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IL-10 tested as negative control; does not protect endothelial cells from complement or apoptosis.
"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."
Human interleukin 10 suppresses production of inflammatory mediators by LPS-stimulated equine peritoneal macrophages.
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IL-10 suppresses inflammatory mediator production in LPS-stimulated macrophages.
"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."
Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanism.
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IL-10 regulates TACE/ADAM-17 ectodomain proteolysis activity.
"In the presence of IL-10, TNF-alpha production and activation of surface TACE was significantly inhibited."
Eis (enhanced intracellular survival) protein of Mycobacterium tuberculosis disturbs the cross regulation of T-cells.
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IL-10 involved in T cell cross-regulation during M. tuberculosis infection.
"Treatment of T-cells with Eis inhibits ERK1/2, JAK pathway, and subsequent production of tumor necrosis factor-alpha and interleukin-4. On the contrary, there is increased production of interferon-gamma and interleukin-10"
Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes.
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IL-10 identified as a potent growth and differentiation factor for activated B cells.
"human and viral IL-10 stimulate DNA replication of B lymphocytes activated either via their antigen receptor or via their CD40 antigen."
Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheumatoid arthritis patients.
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IL-10 and IL-6 genetic interaction in B cell function and immunoglobulin/plasma cell differentiation.
"Besides blocking B-cell receptor-induced proliferation, CR1 inhibits the differentiation of B cells to plasmablasts and their immunoglobulin production."
Deep research synthesis of IL-10 literature
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IL-10 signals through a heterotetrameric receptor of two IL-10RA (ligand-binding) and two IL-10RB (shared signal-transducing) chains coupled to JAK1/TYK2 and STAT3, which is the basis for treating interleukin-10 receptor binding as the core molecular function.
"IL-10 binds a heterotetrameric IL-10 receptor composed of two IL-10RA (IL-10R1; ligand-binding) and two IL-10RB (IL-10R2; shared signal-transducing) chains, predominantly on hematopoietic cells"
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The primary biological role is suppression of inflammatory gene programs, supporting negative regulation of inflammatory response as a core process rather than one of the many peripheral responses in the IEA/ISS set.
"IL-10 is a master anti-inflammatory cytokine that limits duration/intensity of innate and adaptive responses."
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IL-10's immunostimulatory effects (e.g. on CD8+ T cells) are genuine but concentration- and context-dependent, which is why proliferative/stimulatory annotations are retained as non-core rather than accepted as core functions.
"illustrating concentration- and context-dependent pleiotropy within the same receptor pathway"