Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Automatic assignment of GO terms using logical inference, based on inter-ontology links
Combined Automated Annotation using Multiple IEA Methods
Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12
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IL-23 uniquely stimulates memory T cell proliferation and promotes IFN-gamma production in activated T cells.
"IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells."
A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.
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Identified IL23R as the IL-23-specific receptor subunit. IL23R pairs with IL12RB1 to form the functional IL-23 receptor. IL23R constitutively associates with JAK2 and, upon IL-23 binding, recruits STAT3. IL-23 activates JAK2, TYK2, STAT1, STAT3, STAT4, and STAT5 but with weaker STAT4 activation than IL-12. IL23R is expressed on NK cells, T cells, monocytes, and dendritic cells.
"IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits. Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R."
Regulation of virus-induced IL-12 and IL-23 expression in human macrophages
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Sendai virus induces IL-23 production in macrophages, promoting IFN-gamma production in NK cells for antiviral defense.
"Sendai virus stimulates the expression of p19 and p40 mRNAs in macrophages. Furthermore, it enhances p35 mRNA expression and the production of IL-12. Influenza A virus, in contrast, fails to stimulate IL-12 or IL-23 expression in macrophages. IL-12 and IL-23 contribute to the IFN-gamma-inducing activity that cell culture supernatant from Sendai virus-infected macrophages show in NK-92 cells."
Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development
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Gram-negative bacteria prime dendritic cells for enhanced IL-23 production, driving Th1 development.
"all Gram-negative bacteria (GnB) primed moDC for enhanced Th1 cell development, which was dependent on IL-12 and an additional unidentified cofactor. Strikingly, GnB-matured moDC expressed elevated levels of p19 and p28 mRNA, the critical subunits of IL-23 and IL-27, respectively, suggesting that the IL-12 family members may jointly be responsible for their Th1-driving capacity."
Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells.
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IL-23 enhances IL-17 secretion by human T cells while IL-12 specifically inhibits IL-17 production, establishing divergent roles in Th17 biology.
"IL-23 enhanced IL-17 secretion, as did IL-2, IL-15, IL-18 and IL-21. In contrast, IL-12 mediated specific inhibition of IL-17 production. These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion."
IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production
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IL-23 suppression in dendritic cells increases IL-10 and decreases TNF-alpha production.
"Inhibition of IL-23 and IL-12 was associated with increased IL-10 and decreased TNF-alpha production. Furthermore, transfected DCs were poor allostimulators in the MLR."
A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.
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IL23R R381Q variant (rs11209026) is strongly protective against Crohn's disease and ulcerative colitis.
"An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis."
IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats
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IL-23 promotes osteoclastogenesis via IL-17 induction and elevates IL-17/IFN-gamma ratio in activated T cells.
"This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction."
IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function differentially from IL-12
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IL-23 and IL-18 synergistically promote IFN-gamma production in NKT cells but not NK cells, supporting early immune activation.
"Our findings show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells. In contrast, IL-12 together with IL-18-induced secretion of IFN-gamma in both populations."
Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells
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Salmonella-induced IL-23 drives IFN-gamma and GM-CSF production through CD56+ cells, enabling monocyte IL-12 production.
"The findings implicate a positive feedback loop in which IL-23 can enhance its release via induction of IFN-gamma and GM-CSF. The IL-23 induced cytokines allow for the subsequent production of IL-12 and amplify the IFN-gamma production in the type-1 cytokine pathway."
Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
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PX-FERM proteins bind transmembrane cargos including cytokine receptors for endosomal sorting.
"the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins."
A proteome-scale map of the human interactome network.
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High-throughput Y2H screen identifying ~14,000 binary protein-protein interactions including IL23R-C1D.
"Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ?30% larger than what is available from small-scale studies published in the literature in the last few decades."
Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1.
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Crystal structure of IL-23 bound to IL23R reveals binding exclusively through the N-terminal Ig domain, which restructures p19 to enable IL12RB1 recruitment.
"revealed that IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. The structural and functional hotspot of this interaction partially restructured the helical IL-23p19 subunit of IL-23 and restrained its IL-12p40 subunit to cooperatively bind the shared receptor IL-12Rβ1 with high affinity."
Interleukin-23 binds interleukin-23 receptor
Expression of STAT3-upregulated plasma membrane proteins
STAT3, STAT4 are phosphorylated by p-JAK2, p-TYK2 in IL23:IL23 receptor
STAT4 binds p-Y-IL23R in IL23:IL23 receptor
p-Y693-STAT4, p-Y705-STAT3 dissociate from IL23:IL23 receptor
Deep research report on IL23R
GOA annotations for IL23R
OpenScientist hypothesis report for IL23R prolactin receptor activity
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OpenScientist refuted the IL23R prolactin receptor activity hypothesis and recommended removing GO:0004925 as erroneous phylogenetic propagation.
"The GO:0004925 annotation should be removed as an erroneous phylogenetic propagation."