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Gene Review

IL23A  -  interleukin 23, alpha subunit p19

Homo sapiens

Synonyms: IL-23, IL-23 subunit alpha, IL-23-A, IL-23A, IL-23p19, ...
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Disease relevance of IL23A


High impact information on IL23A


Chemical compound and disease context of IL23A


Biological context of IL23A

  • Despite an extensive analysis in 30 individuals, variations located in the exons and in the 5' and 3' UTR regions of IL23A gene were not found in any case [13].
  • These findings indicate that (i) Mphi-1 and Mphi-2 play opposing roles in cellular immunity and (ii) IL-23 rather than IL-12 is the primary type 1 cytokine produced by activated proinflammatory Mphi-1 [14].
  • We then transfected monocyte-derived DCs from healthy donors with antisense oligonucleotides specific for the IL-23p19 and IL-12p35 genes and found potent suppression of gene expression and blockade of bioactive IL-23 and IL-12 production without affecting cellular viability or DCs maturation [3].
  • Results showed a nearly 300-fold up-regulation of transcripts for the p19 subunit of IL-23, and a nearly 18-fold up-regulation for the p40 subunit of IL-12 [15].
  • This phenotype results from the combined lack of IL-12 and IL-23 signaling as both cytokine receptors share IL-12Rbeta1 [16].

Anatomical context of IL23A

  • Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells [17].
  • Anti-IL-12Rbeta1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains [17].
  • Activated dendritic cells produced both IL-12 and IL-23, but unlike Mphi-1 they slightly reduced their IL-23 secretion after addition of IFN-gamma [14].
  • Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria [14].
  • Immunostaining of skin sections confirmed expression of both subunits of IL-23 by keratinocytes in situ and also revealed expression of this cytokine in the dermal compartment [18].

Associations of IL23A with chemical compounds

  • The 15-deoxy-Delta(12,14)-PGJ(2) potently suppressed IL-12p40, IL-23, and IL-27p28 production by primary astrocytes, whereas rosiglitazone suppressed IL-23 and IL-27p28, but not IL-12p40 in these cells [19].
  • Serum Amyloid A Is an Endogenous Ligand That Differentially Induces IL-12 and IL-23 [20].
  • The supernatant of LPS-stimulated DC induced the secretion of IL-17 by polyclonally activated neonatal CD8(+) T cells, confirming the IL-23 bioactivity [21].
  • Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN-gamma-, IL-12-, and IL-23-dependent pathway defects [22].
  • The effects of pp60v-src on cell fate and cell-cell adhesion could be mimicked by direct modulation of Ca+(+)-dependent cell-cell contact during RA induction of normal P19 cells [8].

Regulatory relationships of IL23A

  • 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 [23].
  • IL-23 was expressed mainly by dermal cells and increased p40 immunoreactivity was visualized in large dermal cells in the lesions [2].
  • We report here that HP-NAP is a TLR2 agonist able to induce the expression of IL-12 and IL-23 by neutrophils and monocytes [24].
  • Here, we show that IL-23 induces IL-17 in the lung and IL-17 is required during antigen sensitization to develop allergic asthma, as shown in IL-17R-deficient mice [25].
  • Thus, in a human Th1-mediated disease, blockade of APC cytokines by anti-IL-12p40 down-regulates expression of type 1 cytokines and chemokines that are downstream of IL-12/IL-23, and also IL-12/IL-23 themselves, with a pattern indicative of coordinated deactivation of APCs and Th1 cells [26].
  • The IFN-gamma produced by LPMCs triggered further abnormal macrophage differentiation with an IL-23-hyperproducing phenotype [27].

Other interactions of IL23A

  • The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively [17].
  • Type-1 cytokines, particularly gamma interferon (IFN-gamma), interleukin-12 (IL-12), and IL-23, the major cytokines that regulate IFN-gamma production, are essential in CMI [1].
  • In contrast, activated Mphi-2 produced neither IL-23 nor IL-12 but predominantly secreted IL-10 [14].
  • Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4 [28].
  • In conclusion, this is the first report demonstrating that IL-23 p19 mRNA is inducible in colonic myofibroblasts by IL-1beta and TNF-alpha [29].

Analytical, diagnostic and therapeutic context of IL23A

  • Low but significant levels of the heterodimeric IL-23 protein could be detected in cell lysates and supernatants from stimulated keratinocytes by immunoblotting and ELISA [18].
  • Only histological responders showed marked reductions in the tissue expression of inflammatory genes IFN-gamma, signal transducer and activator of transcription 1, monokine induced by IFN-gamma, inducible NO synthase, IL-8, and IL-23 subunits [30].
  • Upon specific vaccination, however, systemic IL-23 greatly increased the relative and absolute numbers of vaccine-induced CD8(+) T cells and enhanced their effector function at the tumor site [31].
  • In this study we tested the immunological and antitumor effects of the proinflammatory cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma [31].
  • Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation [32].


  1. Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function. van de Vosse, E., Lichtenauer-Kaligis, E.G., van Dissel, J.T., Ottenhoff, T.H. Immunogenetics (2003) [Pubmed]
  2. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. Lee, E., Trepicchio, W.L., Oestreicher, J.L., Pittman, D., Wang, F., Chamian, F., Dhodapkar, M., Krueger, J.G. J. Exp. Med. (2004) [Pubmed]
  3. 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. Vaknin-Dembinsky, A., Balashov, K., Weiner, H.L. J. Immunol. (2006) [Pubmed]
  4. IL-23: a master regulator in Crohn disease. Neurath, M.F. Nat. Med. (2007) [Pubmed]
  5. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Minegishi, Y., Saito, M., Morio, T., Watanabe, K., Agematsu, K., Tsuchiya, S., Takada, H., Hara, T., Kawamura, N., Ariga, T., Kaneko, H., Kondo, N., Tsuge, I., Yachie, A., Sakiyama, Y., Iwata, T., Bessho, F., Ohishi, T., Joh, K., Imai, K., Kogawa, K., Shinohara, M., Fujieda, M., Wakiguchi, H., Pasic, S., Abinun, M., Ochs, H.D., Renner, E.D., Jansson, A., Belohradsky, B.H., Metin, A., Shimizu, N., Mizutani, S., Miyawaki, T., Nonoyama, S., Karasuyama, H. Immunity (2006) [Pubmed]
  6. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Uhlig, H.H., McKenzie, B.S., Hue, S., Thompson, C., Joyce-Shaikh, B., Stepankova, R., Robinson, N., Buonocore, S., Tlaskalova-Hogenova, H., Cua, D.J., Powrie, F. Immunity (2006) [Pubmed]
  7. Interleukin-17 family members and inflammation. Kolls, J.K., Lindén, A. Immunity (2004) [Pubmed]
  8. pp60src tyrosine kinase modulates P19 embryonal carcinoma cell fate by inhibiting neuronal but not epithelial differentiation. Schmidt, J.W., Brugge, J.S., Nelson, W.J. J. Cell Biol. (1992) [Pubmed]
  9. Substrates and inhibitors of human T-cell leukemia virus type I protease. Ding, Y.S., Rich, D.H., Ikeda, R.A. Biochemistry (1998) [Pubmed]
  10. Hepatitis B e antigen polypeptides isolated from sera of individuals infected with hepatitis B virus: comparison with HBeAg polypeptide derived from Dane particles. Takahashi, K., Imai, M., Gotanda, T., Sano, T., Oinuma, A., Mishiro, S., Miyakawa, Y., Mayumi, M. J. Gen. Virol. (1980) [Pubmed]
  11. The role of actin in the apoptotic cell death of P19 embryonal carcinoma cells. Neradil, J., Veselská, R., Svoboda, A. Int. J. Oncol. (2005) [Pubmed]
  12. Methylmercury alters Eph and ephrin expression during neuronal differentiation of P19 embryonal carcinoma cells. Wilson, D.T., Polunas, M.A., Zhou, R., Halladay, A.K., Lowndes, H.E., Reuhl, K.R. Neurotoxicology (2005) [Pubmed]
  13. Interleukin 12 (IL12B), interleukin 12 receptor (IL12RB1) and interleukin 23 (IL23A) gene polymorphism in systemic lupus erythematosus. Sánchez, E., Morales, S., Paco, L., López-Nevot, M.A., Hidalgo, C., Jiménez-Alonso, J., Torres, B., González-Gay, M.A., Callejas, J.L., Ortego-Centeno, N., Sánchez-Roman, J., González-Escribano, M.F., Martín, J. Rheumatology (Oxford, England) (2005) [Pubmed]
  14. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Verreck, F.A., de Boer, T., Langenberg, D.M., Hoeve, M.A., Kramer, M., Vaisberg, E., Kastelein, R., Kolk, A., de Waal-Malefyt, R., Ottenhoff, T.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  15. Francisella tularensis Induces IL-23 Production in Human Monocytes. Butchar, J.P., Rajaram, M.V., Ganesan, L.P., Parsa, K.V., Clay, C.D., Schlesinger, L.S., Tridandapani, S. J. Immunol. (2007) [Pubmed]
  16. Retroviral-mediated gene transfer restores IL-12 and IL-23 signaling pathways in T cells from IL-12 receptor beta1-deficient patients. Bosticardo, M., Witte, I., Fieschi, C., Novelli, F., Casanova, J.L., Candotti, F. Mol. Ther. (2004) [Pubmed]
  17. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. Parham, C., Chirica, M., Timans, J., Vaisberg, E., Travis, M., Cheung, J., Pflanz, S., Zhang, R., Singh, K.P., Vega, F., To, W., Wagner, J., O'Farrell, A.M., McClanahan, T., Zurawski, S., Hannum, C., Gorman, D., Rennick, D.M., Kastelein, R.A., de Waal Malefyt, R., Moore, K.W. J. Immunol. (2002) [Pubmed]
  18. In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin. Piskin, G., Sylva-Steenland, R.M., Bos, J.D., Teunissen, M.B. J. Immunol. (2006) [Pubmed]
  19. Peroxisome Proliferator-Activated Receptor-{gamma} Agonists Suppress the Production of IL-12 Family Cytokines by Activated Glia. Xu, J., Drew, P.D. J. Immunol. (2007) [Pubmed]
  20. Serum Amyloid A Is an Endogenous Ligand That Differentially Induces IL-12 and IL-23. He, R., Shepard, L.W., Chen, J., Pan, Z.K., Ye, R.D. J. Immunol. (2006) [Pubmed]
  21. Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns. Vanden Eijnden, S., Goriely, S., De Wit, D., Goldman, M., Willems, F. Eur. J. Immunol. (2006) [Pubmed]
  22. Gamma interferon is dispensable for neopterin production in vivo. Sghiri, R., Feinberg, J., Thabet, F., Dellagi, K., Boukadida, J., Ben Abdelaziz, A., Casanova, J.L., Barbouche, M.R. Clin. Diagn. Lab. Immunol. (2005) [Pubmed]
  23. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Oppmann, B., Lesley, R., Blom, B., Timans, J.C., Xu, Y., Hunte, B., Vega, F., Yu, N., Wang, J., Singh, K., Zonin, F., Vaisberg, E., Churakova, T., Liu, M., Gorman, D., Wagner, J., Zurawski, S., Liu, Y., Abrams, J.S., Moore, K.W., Rennick, D., de Waal-Malefyt, R., Hannum, C., Bazan, J.F., Kastelein, R.A. Immunity (2000) [Pubmed]
  24. The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. Amedei, A., Cappon, A., Codolo, G., Cabrelle, A., Polenghi, A., Benagiano, M., Tasca, E., Azzurri, A., D'Elios, M.M., Del Prete, G., de Bernard, M. J. Clin. Invest. (2006) [Pubmed]
  25. Interleukin-17 is a negative regulator of established allergic asthma. Schnyder-Candrian, S., Togbe, D., Couillin, I., Mercier, I., Brombacher, F., Quesniaux, V., Fossiez, F., Ryffel, B., Schnyder, B. J. Exp. Med. (2006) [Pubmed]
  26. An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis. Toichi, E., Torres, G., McCormick, T.S., Chang, T., Mascelli, M.A., Kauffman, C.L., Aria, N., Gottlieb, A.B., Everitt, D.E., Frederick, B., Pendley, C.E., Cooper, K.D. J. Immunol. (2006) [Pubmed]
  27. Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. Kamada, N., Hisamatsu, T., Okamoto, S., Chinen, H., Kobayashi, T., Sato, T., Sakuraba, A., Kitazume, M.T., Sugita, A., Koganei, K., Akagawa, K.S., Hibi, T. J. Clin. Invest. (2008) [Pubmed]
  28. Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Watford, W.T., Hissong, B.D., Bream, J.H., Kanno, Y., Muul, L., O'Shea, J.J. Immunol. Rev. (2004) [Pubmed]
  29. Interleukin-1beta and tumor necrosis factor-alpha upregulate interleukin-23 subunit p19 gene expression in human colonic subepithelial myofibroblasts. Zhang, Z., Andoh, A., Yasui, H., Inatomi, O., Hata, K., Tsujikawa, T., Kitoh, K., Takayanagi, A., Shimizu, N., Fujiyama, Y. Int. J. Mol. Med. (2005) [Pubmed]
  30. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Chamian, F., Lowes, M.A., Lin, S.L., Lee, E., Kikuchi, T., Gilleaudeau, P., Sullivan-Whalen, M., Cardinale, I., Khatcherian, A., Novitskaya, I., Wittkowski, K.M., Krueger, J.G. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  31. Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant. Overwijk, W.W., de Visser, K.E., Tirion, F.H., de Jong, L.A., Pols, T.W., van der Velden, Y.U., van den Boorn, J.G., Keller, A.M., Buurman, W.A., Theoret, M.R., Blom, B., Restifo, N.P., Kruisbeek, A.M., Kastelein, R.A., Haanen, J.B. J. Immunol. (2006) [Pubmed]
  32. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. Becker, C., Dornhoff, H., Neufert, C., Fantini, M.C., Wirtz, S., Huebner, S., Nikolaev, A., Lehr, H.A., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Galle, P.R., Karow, M., Neurath, M.F. J. Immunol. (2006) [Pubmed]
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