Genomes and Genes
Gene Symbol: IL 23R
Description: interleukin 23 receptor
Alias: IL-23R, interleukin-23 receptor, IL-23 receptor
Products: IL 23R
- Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002;168:5699-708 pubmed..The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2. ..
- Cox J, Kljavin N, Ota N, Leonard J, Roose Girma M, Diehl L, et al. Opposing consequences of IL-23 signaling mediated by innate and adaptive cells in chemically induced colitis in mice. Mucosal Immunol. 2012;5:99-109 pubmed publisher..In summary, we provide evidence for opposing consequences of IL-23R on innate and adaptive lymphoid cells in murine colitis. ..
- Rachitskaya A, Hansen A, Horai R, Li Z, Villasmil R, Luger D, et al. Cutting edge: NKT cells constitutively express IL-23 receptor and RORgammat and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J Immunol. 2008;180:5167-71 pubmed..These data suggest an important biological role for innate IL-17 production by NKT cells that is rapid and precedes the adaptive IL-17 response. ..
- Arbelaez C, Glatigny S, Duhen R, Eberl G, Oukka M, Bettelli E. IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets Involved in Experimental Autoimmune Encephalomyelitis. J Immunol. 2015;195:1974-83 pubmed publisher..Together, these data address the contribution of IL-23/IL-23R and IL-7/IL-7R signaling in Th17 and Th1 cell dynamics during CNS autoimmunity. ..
- Zhou V, Agle K, Chen X, Beres A, Komorowski R, Belle L, et al. A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease. J Clin Invest. 2016;126:3541-55 pubmed publisher..Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10-regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. ..
- Wang M, Zhong D, Zheng Y, Li H, Chen H, Ma S, et al. Damage effect of interleukin (IL)-23 on oxygen-glucose-deprived cells of the neurovascular unit via IL-23 receptor. Neuroscience. 2015;289:406-16 pubmed publisher..These results not only help us better understand the role of IL-23/IL-23R in brain ischemia, but also provide a potential therapeutic target in stroke. ..
- Lee Y, Awasthi A, Yosef N, Quintana F, Xiao S, Peters A, et al. Induction and molecular signature of pathogenic TH17 cells. Nat Immunol. 2012;13:991-9 pubmed publisher..Moreover, TGF-?3-induced T(H)17 cells were functionally and molecularly distinct from TGF-?1-induced T(H)17 cells and had a molecular signature that defined pathogenic effector T(H)17 cells in autoimmune disease. ..
- Ermann J, Staton T, Glickman J, de Waal Malefyt R, Glimcher L. Nod/Ripk2 signaling in dendritic cells activates IL-17A-secreting innate lymphoid cells and drives colitis in T-bet-/-.Rag2-/- (TRUC) mice. Proc Natl Acad Sci U S A. 2014;111:E2559-66 pubmed publisher..Our data provide insight into the complex network of interactions between IL-17A-secreting ILCs and other components of the innate immune system in the development of colitis. ..
- Lee J, Tato C, Joyce Shaikh B, Gulen M, Gulan F, Cayatte C, et al. Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability. Immunity. 2015;43:727-38 pubmed publisher..These results suggest that IL-17-producing ?? T cells are important for the maintenance and protection of epithelial barriers in the intestinal mucosa. ..
- Shih V, Cox J, Kljavin N, Dengler H, Reichelt M, Kumar P, et al. Homeostatic IL-23 receptor signaling limits Th17 response through IL-22-mediated containment of commensal microbiota. Proc Natl Acad Sci U S A. 2014;111:13942-7 pubmed publisher..Thus, barrier defects generate a systemic environment that facilitates Th17 development. ..
- Meyer zu Horste G, Wu C, Wang C, Cong L, Pawlak M, Lee Y, et al. RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression. Cell Rep. 2016;16:392-404 pubmed publisher..We thus find that Notch signaling influences the development of pathogenic and non-pathogenic Th17 cells by reciprocally regulating IL-23R and IL-10 expression. ..
- Malik S, Sadhu S, Elesela S, Pandey R, Chawla A, Sharma D, et al. Transcription factor Foxo1 is essential for IL-9 induction in T helper cells. Nat Commun. 2017;8:815 pubmed publisher..The transcription factor Foxo1 can control regulatory T cell and Th1 function. Here the authors show that Foxo1 is also critical for IL-9 production by Th9 cells and other IL-9-producing cells. ..
- Kara E, McKenzie D, Bastow C, Gregor C, Fenix K, Ogunniyi A, et al. CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells. Nat Commun. 2015;6:8644 pubmed publisher..Thus, our data identify a unique cell surface signature, trafficking mechanism and T-cell intrinsic regulators of GM-CSF/IFNÎ³-producing Th17 cells. ..
- Banerjee A, Bhattacharya P, Dagur P, Karmakar S, Ismail N, Joshi A, et al. Live Attenuated Leishmania donovani Centrin Gene-Deleted Parasites Induce IL-23-Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a Murine Model. J Immunol. 2018;200:163-176 pubmed publisher..This study unveiled the role of IL-23-dependent IL-17 induction in LdCen-/- parasite-induced immunity and subsequent protection against visceral leishmaniasis. ..
- Singh T, Zhang H, Borek I, Wolf P, Hedrick M, Singh S, et al. Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation. Nat Commun. 2016;7:13581 pubmed publisher..Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells. ..
- Peters A, Pitcher L, Sullivan J, Mitsdoerffer M, Acton S, Franz B, et al. Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation. Immunity. 2011;35:986-96 pubmed publisher..Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ. ..
- Krausgruber T, Schiering C, Adelmann K, Harrison O, Chomka A, Pearson C, et al. T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell responses in the intestine. Nat Commun. 2016;7:11627 pubmed publisher..Our study identifies T-bet as a key modulator of IL-23-driven colitogenic responses in the intestine and has important implications for understanding of heterogeneity among inflammatory bowel disease patients. ..
- Sefik E, Geva Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire A, et al. MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of ROR?? regulatory T cells. Science. 2015;349:993-7 pubmed publisher..Ror?, and the T(regs) that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Ror? results in very different outcomes even in closely related cell types. ..
- Yang J, Xu L. Elevated IL-23R Expression and Foxp3+Rorgt+ Cells in Intestinal Mucosa During Acute and Chronic Colitis. Med Sci Monit. 2016;22:2785-92 pubmed..Our study highlights the importance of IL-23R expression level and the instability of Foxp3+ regulatory T cells in the development of inflammatory bowel diseases. ..
- Aychek T, Mildner A, Yona S, Kim K, Lampl N, Reich Zeliger S, et al. IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology. Nat Commun. 2015;6:6525 pubmed publisher..Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNÎ³-producing former TH17 cells and fatal immunopathology. ..
- Li H, Hsu H, Wu Q, Yang P, Li J, Luo B, et al. IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and ROR?t. Nat Commun. 2014;5:4259 pubmed publisher..These results extend the action of IL-23 beyond its peripheral effects to a unique role in TCR-mediated negative selection including elimination of natural T regulatory cells in the thymus. ..
- Riol Blanco L, Ordovas Montanes J, Perro M, Naval E, Thiriot A, Alvarez D, et al. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature. 2014;510:157-61 pubmed publisher..These findings indicate that TRPV1(+)Nav1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses. ..
- Chaudhry A, Samstein R, Treuting P, Liang Y, Pils M, Heinrich J, et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity. 2011;34:566-78 pubmed publisher..Thus, Treg cells limit Th17 cell inflammation by serving as principal amplifiers of negative regulatory circuits operating in immune effector cells. ..
- Kishi Y, Kondo T, Xiao S, Yosef N, Gaublomme J, Wu C, et al. Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity. J Exp Med. 2016;213:2489-2501 pubmed..PROCR thus does not globally inhibit Th17 responses but could be targeted to selectively inhibit proinflammatory Th17 cells. ..
- Duhen R, Glatigny S, Arbelaez C, Blair T, Oukka M, Bettelli E. Cutting edge: the pathogenicity of IFN-Î³-producing Th17 cells is independent of T-bet. J Immunol. 2013;190:4478-82 pubmed publisher..Whereas T-bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell-mediated autoimmunity. Our results suggest the existence of different epigenetic programs that regulate IFN-Î³ expression in Th1 and Th17 cells. ..
- Grivennikov S, Wang K, Mucida D, Stewart C, Schnabl B, Jauch D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012;491:254-8 pubmed publisher..We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth...
- Morishima N, Mizoguchi I, Takeda K, Mizuguchi J, Yoshimoto T. TGF-beta is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23. Biochem Biophys Res Commun. 2009;386:105-10 pubmed publisher..These results suggest that the induction of IL-23R and Th17 differentiation by IL-6 and IL-23 is mediated through endogenously produced TGF-beta. ..
- Du F, Garg A, Kosar K, Majumder S, Kugler D, Mir G, et al. Inflammatory Th17 Cells Express Integrin ?v?3 for Pathogenic Function. Cell Rep. 2016;16:1339-1351 pubmed publisher..Hence, integrin ?3 is required for Th17 cell-mediated autoimmune CNS inflammation. ..
- Kyttaris V, Zhang Z, Kuchroo V, Oukka M, Tsokos G. Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol. 2010;184:4605-9 pubmed publisher..The presented experiments document the importance of IL-23R-mediated signaling in the development of lupus nephritis and urge the consideration of proper biologics for the treatment of the disease. ..
- Purwar R, Schlapbach C, Xiao S, Kang H, Elyaman W, Jiang X, et al. Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells. Nat Med. 2012;18:1248-53 pubmed publisher..These results suggest a role for IL-9 in tumor immunity and offer insight into potential therapeutic strategies. ..
- Franke M, SchrÃ¶der J, Monhasery N, Ackfeld T, Hummel T, Rabe B, et al. Human and Murine Interleukin 23 Receptors Are Novel Substrates for A Disintegrin and Metalloproteases ADAM10 and ADAM17. J Biol Chem. 2016;291:10551-61 pubmed publisher..Finally, interaction studies identified domains 1 and 3 of the IL-23R as the main ADAM17 binding sites. In summary, we describe human and murine IL-23R as novel targets for protein ectodomain shedding by ADAM10 and ADAM17. ..
- Haas J, Nistala K, Petermann F, Saran N, Chennupati V, Schmitz S, et al. Expression of miRNAs miR-133b and miR-206 in the Il17a/f locus is co-regulated with IL-17 production in ?? and ?? T cells. PLoS ONE. 2011;6:e20171 pubmed publisher..Notably, the specific co-regulation of miR-133b and miR-206 with the Il17a/f locus also extended to human Th17 cells. This qualifies expression of miR-133b and miR-206 in T cells as novel biomarkers for Th17-type immune reactions. ..
- Liang D, Zuo A, Shao H, Born W, O Brien R, Kaplan H, et al. IL-23 receptor expression on ?? T cells correlates with their enhancing or suppressive effects on autoreactive T cells in experimental autoimmune uveitis. J Immunol. 2013;191:1118-25 pubmed publisher..The expression of variable IL-23R levels allows ?? T cells to have different regulatory effects on adaptive immune responses, conceivably as a result of ?? and ?? T cells competing for IL-23. ..
- Newcomb D, Cephus J, Boswell M, Fahrenholz J, Langley E, Feldman A, et al. Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma. J Allergy Clin Immunol. 2015;136:1025-34.e11 pubmed publisher..17Î²-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men. ..
- Eken A, Singh A, Treuting P, Oukka M. IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism. Mucosal Immunol. 2014;7:143-54 pubmed publisher..Collectively, our results reveal that similar to its controversial role during chronic or adaptive colitis, IL-22 may also have opposite roles in innate colitis pathogenesis in a context and insult-dependent manner. ..
- Yang Y, Torchinsky M, Gobert M, Xiong H, Xu M, Linehan J, et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature. 2014;510:152-6 pubmed publisher..These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines. ..
- Wang C, Yosef N, Gaublomme J, Wu C, Lee Y, Clish C, et al. CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity. Cell. 2015;163:1413-27 pubmed publisher..Our study identifies CD5L as a critical regulator of the Th17 cell functional state and highlights the importance of lipid metabolism in balancing immune protection and disease induced by T cells. ..
- Punkenburg E, Vogler T, BÃ¼ttner M, Amann K, Waldner M, Atreya R, et al. Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer. Gut. 2016;65:1139-50 pubmed publisher..Batf-dependent IL-23R(+) T cells represent a potential future therapeutic target limiting CRC progression. ..
- Singh A, Eken A, Fry M, Bettelli E, Oukka M. DOCK8 regulates protective immunity by controlling the function and survival of ROR?t+ ILCs. Nat Commun. 2014;5:4603 pubmed publisher..Our studies reveal an unsuspected role of DOCK8 for the function, generation and survival of ROR?t(+) ILCs. ..
- Aden K, Rehman A, Falk Paulsen M, Secher T, Kuiper J, Tran F, et al. Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation. Cell Rep. 2016;16:2208-2218 pubmed publisher..The study identifies a critical barrier-protective immune pathway that originates from, and is orchestrated by, IL-23R signaling in intestinal epithelial cells. ..
- Yoon J, Leyva Castillo J, Wang G, Galand C, Oyoshi M, Kumar L, et al. IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med. 2016;213:2147-66 pubmed publisher..We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD. ..
- Wang C, Wu L, Bulek K, Martin B, Zepp J, Kang Z, et al. The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90. Nat Immunol. 2013;14:72-81 pubmed publisher..In the absence of IL-17 signaling, IL-22 was the main contributor to skin inflammation, which provides a molecular mechanism for the association of Act1(D10N) with psoriasis susceptibility. ..
- Langowski J, Zhang X, Wu L, Mattson J, Chen T, Smith K, et al. IL-23 promotes tumour incidence and growth. Nature. 2006;442:461-5 pubmed..We show that IL-23 is an important molecular link between tumour-promoting pro-inflammatory processes and the failure of the adaptive immune surveillance to infiltrate tumours. ..
- Grifka Walk H, Giles D, Segal B. IL-12-polarized Th1 cells produce GM-CSF and induce EAE independent of IL-23. Eur J Immunol. 2015;45:2780-6 pubmed publisher..These data provide definitive evidence that autoimmune disease can be driven by distinct CD4(+) T-helper-cell subsets and polarizing factors. ..
- Floss D, Mrotzek S, Klöcker T, Schröder J, Grötzinger J, Rose John S, et al. Identification of canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the intracellular domain of the interleukin 23 receptor. J Biol Chem. 2013;288:19386-400 pubmed publisher..In summary, we characterized IL-23-dependent signal transduction with a focus on STAT3 phosphorylation and identified canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the IL-23R. ..
- Laird R, Wolf B, Princiotta M, Hayes S. ?? T cells acquire effector fates in the thymus and differentiate into cytokine-producing effectors in a Listeria model of infection independently of CD28 costimulation. PLoS ONE. 2013;8:e63178 pubmed publisher..Together, these data not only demonstrate an enhanced glucose metabolism in ?? T cells but also provide an explanation for why ?? T cells are less dependent on CD28 costimulation than ?? T cells. ..