Genomes and Genes
Gene Symbol: Il23a
Description: interleukin 23, alpha subunit p19
Alias: IL-23, p19, interleukin-23 subunit alpha, IL-23 subunit alpha, IL-23-A, IL-23p19, interleukin-23 subunit p19
- Nguyen C, Hu M, Li Y, Stewart C, Peck A. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjögren's syndrome: findings in humans and mice. Arthritis Rheum. 2008;58:734-43 pubmed publisher..NOD-Aec1Aec2 mice and SS patients at the time of disease. A correlation between up-regulated IL-17/IL-23 expression and specific clinical manifestations of SS has yet to be identified. ..
- Khayrullina T, Yen J, Jing H, Ganea D. In vitro differentiation of dendritic cells in the presence of prostaglandin E2 alters the IL-12/IL-23 balance and promotes differentiation of Th17 cells. J Immunol. 2008;181:721-35 pubmed..high IL-23 production in LPS-stimulated DCp is associated with the down-regulation of p35 and the up-regulation of p19 expression, respectively...
- Tanaka S, Yoshimoto T, Naka T, Nakae S, Iwakura Y, Cua D, et al. Natural occurring IL-17 producing T cells regulate the initial phase of neutrophil mediated airway responses. J Immunol. 2009;183:7523-30 pubmed publisher..10 Rag(-/-) mice. These results demonstrate that a novel T cell subset, nTh17, facilitates the early phase of Ag-induced airway responses and host defenses against pathogen invasion before the establishment of acquired immunity. ..
- Mangan P, Harrington L, O Quinn D, Helms W, Bullard D, Elson C, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature. 2006;441:231-4 pubmed..The action of TGF-beta on naive T cells is antagonized by interferon-gamma and IL-4, thus providing a mechanism for divergence of the T(H)1, T(H)2 and T(H)17 lineages. ..
- Cua D, Sherlock J, Chen Y, Murphy C, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744-8 pubmed..The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells...
- Buonocore S, Ahern P, Uhlig H, Ivanov I, Littman D, Maloy K, et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature. 2010;464:1371-5 pubmed publisher..These results identify a previously unrecognized IL-23-responsive innate lymphoid population that mediates intestinal immune pathology and may therefore represent a target in inflammatory bowel disease. ..
- Kullberg M, Jankovic D, Feng C, Hue S, Gorelick P, McKenzie B, et al. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J Exp Med. 2006;203:2485-94 pubmed
- Kleinschek M, Owyang A, Joyce Shaikh B, Langrish C, Chen Y, Gorman D, et al. IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med. 2007;204:161-70 pubmed..Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity. ..
- Thakker P, Leach M, Kuang W, Benoit S, Leonard J, Marusic S. IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis. J Immunol. 2007;178:2589-98 pubmed..wild-type (WT) mice caused indistinguishable disease when adoptively transferred to WT or IL-23-deficient (p19 knockout (KO)) recipient mice, demonstrating that once encephalitogenic cells have been generated, EAE can develop ..
- Lemos H, Grespan R, Vieira S, Cunha T, Verri W, Fernandes K, et al. Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNgamma production. Proc Natl Acad Sci U S A. 2009;106:5954-9 pubmed publisher..We thus provide a mechanism for the pathogenic role of the IL-23/IL-17 axis in RA and also suggest an additional mechanism of action for nonsteroidal anti-inflammatory drugs. ..
- Oppmann B, Lesley R, Blom B, Timans J, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715-25 pubmed..This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, ..
- Lo Re S, Dumoutier L, Couillin I, Van Vyve C, Yakoub Y, Uwambayinema F, et al. IL-17A-producing gammadelta T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis. J Immunol. 2010;184:6367-77 pubmed publisher..Although the acute alveolitis induced by silica is IL-17A dependent, this cytokine appears dispensable for the development of the late inflammatory and fibrotic lung responses to silica. ..
- Chen Y, Langrish C, McKenzie B, Joyce Shaikh B, Stumhofer J, McClanahan T, et al. Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest. 2006;116:1317-26 pubmed..Thus, therapeutic targeting of IL-23 effectively inhibited multiple inflammatory pathways that are critical for driving CNS autoimmune inflammation. ..
- Happel K, Dubin P, Zheng M, Ghilardi N, Lockhart C, Quinton L, et al. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med. 2005;202:761-9 pubmedInterleukin (IL)-23 is a heterodimeric cytokine that shares the identical p40 subunit as IL-12 but exhibits a unique p19 subunit similar to IL-12 p35...
- Hue S, Ahern P, Buonocore S, Kullberg M, Cua D, McKenzie B, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006;203:2473-83 pubmed..These results newly identify IL-23 as a driver of innate immune pathology in the intestine and suggest that selective targeting of IL-23 represents an attractive therapeutic approach in human IBD...
- Cooper A, Kipnis A, Turner J, Magram J, Ferrante J, Orme I. Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present. J Immunol. 2002;168:1322-7 pubmed..This cytokine is composed of the IL-12 p40 subunit and a p19 subunit. In support of a role for this cytokine in protective responses to M...
- Rudner X, Happel K, Young E, Shellito J. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect Immun. 2007;75:3055-61 pubmed..In IL-23p19-/- mice infected with P. carinii, there were fewer effector CD4(+) T cells in the lung tissue. Collectively, these studies indicate that the IL-23-IL-17 axis participates in host defense against P. carinii. ..
- Wakashin H, Hirose K, Maezawa Y, Kagami S, Suto A, Watanabe N, et al. IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. Am J Respir Crit Care Med. 2008;178:1023-32 pubmed publisher..IL-23 and Th17 cells not only induce Th17-cell-mediated neutrophilic airway inflammation but also up-regulate Th2-cell-mediated eosinophilic airway inflammation. ..
- Ferreira M, Whibley N, Mamo A, Siebenlist U, Chan Y, Gaffen S. Interleukin-17-induced protein lipocalin 2 is dispensable for immunity to oral candidiasis. Infect Immun. 2014;82:1030-5 pubmed publisher..Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis. ..
- Munoz M, Heimesaat M, Danker K, Struck D, Lohmann U, Plickert R, et al. Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J Exp Med. 2009;206:3047-59 pubmed publisher..Thus, IL-23 regulates small intestinal inflammation via IL-22 but independent of IL-17. Gelatinases may be useful targets for treatment of intestinal inflammation. ..
- Shichita T, Sugiyama Y, Ooboshi H, Sugimori H, Nakagawa R, Takada I, et al. Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury. Nat Med. 2009;15:946-50 pubmed publisher..We propose that T lymphocytes, including gammadeltaT lymphocytes, could be a therapeutic target for mitigating the inflammatory events that amplify the initial damage in cerebral ischemia. ..
- Ghilardi N, Kljavin N, Chen Q, Lucas S, Gurney A, De Sauvage F. Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice. J Immunol. 2004;172:2827-33 pubmedThe heterodimeric cytokine IL-23 consists of a private cytokine-like p19 subunit and a cytokine receptor-like subunit, p40, which is shared with IL-12...
- Meeks K, Sieve A, Kolls J, Ghilardi N, Berg R. IL-23 is required for protection against systemic infection with Listeria monocytogenes. J Immunol. 2009;183:8026-34 pubmed publisher..These results indicate that during LM infection, IL-23 regulates the production of IL-17A and IL-17F from gammadelta T cells, resulting in optimal liver neutrophil recruitment and enhanced bacterial clearance. ..
- Mise Omata S, Kuroda E, Niikura J, Yamashita U, Obata Y, Doi T. A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription. J Immunol. 2007;179:6596-603 pubmedIL-23 is a heterodimeric cytokine composed of a unique p19 subunit and a common p40 subunit is shared with IL-12. IL-23 promotes the inflammatory response by inducing the expansion of CD4(+) cells producing IL-17...
- Chen Z, Laurence A, Kanno Y, Pacher Zavisin M, Zhu B, Tato C, et al. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A. 2006;103:8137-42 pubmed..We conclude that Socs3 is an essential negative regulator of IL-23 signaling, inhibition of which constrains the generation of Th17 differentiation. ..
- Uhlig H, McKenzie B, Hue S, Thompson C, Joyce Shaikh B, Stepankova R, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity. 2006;25:309-18 pubmed..colitis, but not wasting disease or serum proinflammatory cytokine production, depended on interleukin-23 p19 secretion, whereas interleukin-12 p35 secretion controlled wasting disease and serum cytokine production but not ..
- Kinnebrew M, Buffie C, Diehl G, Zenewicz L, Leiner I, Hohl T, et al. Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity. 2012;36:276-87 pubmed publisher..Thus, CD103(+)CD11b(+) LPDCs, in addition to promoting long-term tolerance to ingested antigens, also rapidly produce IL-23 in response to detection of flagellin in the lamina propria. ..
- Basu R, O Quinn D, Silberger D, Schoeb T, Fouser L, Ouyang W, et al. Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity. 2012;37:1061-75 pubmed publisher..These findings establish Th22 cells as an important component of mucosal antimicrobial host defense. ..
- Murphy C, Langrish C, Chen Y, Blumenschein W, McClanahan T, Kastelein R, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003;198:1951-7 pubmedInterleukin (IL) 23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 affects memory T cell and inflammatory macrophage function through engagement of a novel receptor (IL-23R) on these cells...
- Schulz S, Kohler G, Schütze N, Knauer J, Straubinger R, Chackerian A, et al. Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. J Immunol. 2008;181:7891-901 pubmed..To characterize the role of the related cytokine IL-23, wild-type (WT) C57BL/6 and p19(-/-) mice were infected systemically with an attenuated strain of Salmonella enterica serovar Enteritidis (S...
- El Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol. 2011;12:568-75 pubmed publisher..Such cross-regulation of IL-23 and GM-CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies T(H)17 cells as a crucial source of GM-CSF in autoimmune inflammation. ..
- Zelante T, De Luca A, Bonifazi P, Montagnoli C, Bozza S, Moretti S, et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol. 2007;37:2695-706 pubmed..As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi. ..
- Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, et al. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell. 2009;15:114-23 pubmed publisher..IL-23, which is mainly produced by tumor-associated macrophages, via direct transcriptional activation of the IL-23/p19 gene...
- Godinez I, Raffatellu M, Chu H, Paixao T, Haneda T, Santos R, et al. Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine. Infect Immun. 2009;77:387-98 pubmed publisher..Collectively, our results point to IL-23 as an important player in initiating a T-cell-dependent amplification of inflammatory responses in the intestinal mucosa during serotype Typhimurium infection...
- Liang S, Tan X, Luxenberg D, Karim R, Dunussi Joannopoulos K, Collins M, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006;203:2271-9 pubmed..Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity. ..
- Izcue A, Hue S, Buonocore S, Arancibia Cárcamo C, Ahern P, Iwakura Y, et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity. 2008;28:559-70 pubmed publisher..Taken together, our data indicate that overriding immunosuppressive pathways is an important function of IL-23 in the intestine and could influence not only Th17 cell activity but also other types of immune responses. ..
- Luger D, Silver P, Tang J, Cua D, Chen Z, Iwakura Y, et al. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med. 2008;205:799-810 pubmed publisher..These data also raise the possibility that the nonredundant requirement for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and help provide a balance in the current Th1 versus Th17 paradigm. ..
- 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. ..
- Lieberman L, Cardillo F, Owyang A, Rennick D, Cua D, Kastelein R, et al. IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12. J Immunol. 2004;173:1887-93 pubmed..Together, these studies indicate that IL-12, not IL-23, plays a dominant role in resistance to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited mechanism of resistance to this infection. ..
- Sonnenberg G, Monticelli L, Elloso M, Fouser L, Artis D. CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity. 2011;34:122-34 pubmed publisher..Collectively these data demonstrate that adult CD4(+) LTi cells are a critical source of IL-22 and identify a previously unrecognized function for CD4(+) LTi cells in promoting innate immunity in the intestine. ..
- Hirota K, Duarte J, Veldhoen M, Hornsby E, Li Y, Cua D, et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol. 2011;12:255-63 pubmed publisher..Thus, this model allows the actual functional fate of effector T cells to be related to T(H)17 developmental origin regardless of IL-17 expression. ..
- Becker C, Dornhoff H, Neufert C, Fantini M, Wirtz S, Huebner S, et al. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol. 2006;177:2760-4 pubmed..IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease...
- Sieve A, Meeks K, Lee S, Berg R. A novel immunoregulatory function for IL-23: Inhibition of IL-12-dependent IFN-? production. Eur J Immunol. 2010;40:2236-47 pubmed publisher..Our data suggest that IL-23 may be a key factor in determining the responsiveness of lymphocytes to IL-12 and their subsequent secretion of IFN-?. ..
- Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116:1310-6 pubmed..This pathway may be responsible for chronic intestinal inflammation as well as other chronic autoimmune inflammatory diseases. ..
- Khader S, Guglani L, Rangel Moreno J, Gopal R, Junecko B, Fountain J, et al. IL-23 is required for long-term control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung. J Immunol. 2011;187:5402-7 pubmed publisher..However, mice deficient for the p19 component of IL-23 (Il23a(-/-)) exhibit increased bacterial growth late in infection that is temporally associated with smaller B cell ..
- Huppler A, Conti H, Hernández Santos N, Darville T, Biswas P, Gaffen S. Role of neutrophils in IL-17-dependent immunity to mucosal candidiasis. J Immunol. 2014;192:1745-52 pubmed publisher..Thus, CXCR2(+) and Gr-1(+) neutrophils play a vital role in host defense against OPC. Moreover, defects in the IL-23/17 axis cause a potent but incomplete deficiency in the neutrophil response to oral candidiasis. ..
- Kagami S, Rizzo H, Kurtz S, Miller L, Blauvelt A. IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J Immunol. 2010;185:5453-62 pubmed publisher..In addition, recombinant IL-17A may serve as a potential therapy to enhance healing in individuals with chronic cutaneous candidiasis...
- Zheng Y, Valdez P, Danilenko D, Hu Y, Sa S, Gong Q, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008;14:282-9 pubmed publisher..rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens...
- Khader S, Bell G, Pearl J, Fountain J, Rangel Moreno J, Cilley G, et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol. 2007;8:369-77 pubmed
- Wozniak T, Ryan A, Britton W. Interleukin-23 restores immunity to Mycobacterium tuberculosis infection in IL-12p40-deficient mice and is not required for the development of IL-17-secreting T cell responses. J Immunol. 2006;177:8684-92 pubmed..Therefore, exogenous IL-23 can complement IL-12 deficiency for the initial expansion of Ag-specific T cells and is not essential for the development of potentially protective IL-17-secreting T cells. ..
- Aggarwal S, Ghilardi N, Xie M, De Sauvage F, Gurney A. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910-4 pubmed..These data suggest that during a secondary immune response, IL-23 can promote an activation state with features distinct from the well characterized Th1 and Th2 profiles. ..
- Rizzo H, Kagami S, Phillips K, Kurtz S, Jacques S, Blauvelt A. IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. J Immunol. 2011;186:1495-502 pubmed publisher..IL-17A may represent an attractive therapeutic target in individuals with psoriasis by blocking downstream effects of IL-23. ..
- Cornelissen F, Mus A, Asmawidjaja P, van Hamburg J, Tocker J, Lubberts E. Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORgammat in gammadelta T cells. Arthritis Res Ther. 2009;11:R194 pubmed publisher..Furthermore, IL-23 regulates IL-17A and RORgammat expression in TCRgammadelta T cells in arthritis. These findings indicate that regulating the IL-23 pathway may have therapeutic potential in non-autoimmune arthritis. ..
- Khader S, Partida Sanchez S, Bell G, Jelley Gibbs D, Swain S, Pearl J, et al. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. J Exp Med. 2006;203:1805-15 pubmed..These data define a novel and fundamental role for IL-12p40 in the pathogen-induced activation of pulmonary DCs. ..
- Khader S, Pearl J, Sakamoto K, Gilmartin L, Bell G, Jelley Gibbs D, et al. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol. 2005;175:788-95 pubmed..IL-23 is an IL-12p40-dependent cytokine containing an IL-12p40 subunit covalently bound to a p19 subunit that is implicated in the induction of CD4 T cells associated with autoimmunity and inflammation...
- Wiekowski M, Leach M, Evans E, Sullivan L, Chen S, Vassileva G, et al. Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol. 2001;166:7563-70 pubmedb>p19, a molecule structurally related to IL-6, G-CSF, and the p35 subunit of IL-12, is a subunit of the recently discovered cytokine IL-23...