Interleukin 23
Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene.[1][2] IL-23 is produced by dendritic cells and macrophages. Moreover, IL-23 is stimulated by Danger Signals, including cell debris, and directs memory T cells to Th17 response.
This gene encodes the p19 subunit of the heterodimeric cytokine interleukin 23 (IL23). IL23 is composed of this protein and the p40 subunit of interleukin 12 (IL12B). The receptor of IL23 is formed by the beta 1 subunit of IL12 (IL12RB1) and an IL23 specific subunit, IL23R. Both IL23 and IL12 can activate the transcription activator STAT4, and stimulate the production of interferon-gamma (IFNG). In contrast to IL12, which acts mainly on naive CD4(+) T cells, IL23 preferentially acts on memory CD4(+) T cells.[2]
Interleukin-23 (IL-23) is a heterodimeric cytokine consisting of two subunits, one called p40, which is shared with another cytokine, IL-12, and another called p19 (the IL-23 alpha subunit). In other words, IL-23 is a dimer of p40-S-S-p19. IL-23 is an important part of the inflammatory response against infection. It promotes upregulation of the matrix metalloprotease MMP9, increases angiogenesis and reduces CD8+ T-cell infiltration. Recently, IL-23 has been implicated in the development of cancerous tumors. In conjunction with IL-6 and TGF-β1, IL-23 stimulates naive CD4+ T cells to differentiate into a novel subset of cells called Th17 cells, which are distinct from the classical Th1 and Th2 cells. Th17 cells produce IL-17, a proinflammatory cytokine that enhances T cell priming and stimulates the production of proinflammatory molecules such as IL-1, IL-6, TNF-alpha, NOS-2, and chemokines resulting in inflammation. Knockout mice deficient in either p40 or p19, or in either subunit of the IL-23 receptor (IL-23R and IL12R-β1) develop less severe symptoms of multiple sclerosis and inflammatory bowel disease highlighting the importance of IL-23 in the inflammatory pathway.[3][4]
Interactions
Interleukin 23 has been shown to interact with Interleukin-12 subunit beta.[1]
See also
- CNTO 1275, an experimental therapeutic anti-IL-23 antibody
References
- ^ a b Oppmann B, Lesley R, Blom B, Timans JC, 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 JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (Jan 2001). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12". Immunity 13 (5): 715–25. doi:10.1016/S1074-7613(00)00070-4. PMID 11114383.
- ^ a b "Entrez Gene: IL23A interleukin 23, alpha subunit p19". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51561.
- ^ Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (2006). "IL-23 promotes tumour incidence and growth". Nature 442 (7101): 461–5. doi:10.1038/nature04808. PMID 16688182.
- ^ Kikly K, Liu L, Na S, Sedgwick JD (2006). "The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation". Curr. Opin. Immunol. 18 (6): 670–5. doi:10.1016/j.coi.2006.09.008. PMID 17010592.
Further reading
- Lankford CS, Frucht DM (2003). "A unique role for IL-23 in promoting cellular immunity". J. Leukoc. Biol. 73 (1): 49–56. doi:10.1189/jlb.0602326. PMID 12525561.
- van de Vosse E, Lichtenauer-Kaligis EG, van Dissel JT, Ottenhoff TH (2003). "Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function". Immunogenetics 54 (12): 817–29. doi:10.1007/s00251-002-0534-9. PMID 12671732.
- Kreymborg K, Böhlmann U, Becher B (2006). "IL-23: changing the verdict on IL-12 function in inflammation and autoimmunity". Expert Opin. Ther. Targets 9 (6): 1123–36. doi:10.1517/14728222.9.6.1123. PMID 16300465.
- Peluso I, Pallone F, Monteleone G (2006). "Interleukin-12 and Th1 immune response in Crohn's disease: pathogenetic relevance and therapeutic implication". World J. Gastroenterol. 12 (35): 5606–10. PMID 17007011.
- Prashar Y, Weissman SM (1996). "Analysis of differential gene expression by display of 3' end restriction fragments of cDNAs". Proc. Natl. Acad. Sci. U.S.A. 93 (2): 659–63. doi:10.1073/pnas.93.2.659. PMC 40108. PMID 8570611. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=40108.
- Wiekowski MT, Leach MW, Evans EW et al. (2001). "Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death". J. Immunol. 166 (12): 7563–70. PMID 11390512.
- Parham C, Chirica M, Timans J et al. (2002). "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R". J. Immunol. 168 (11): 5699–708. PMID 12023369.
- Broberg EK, Setälä N, Erälinna JP et al. (2003). "Herpes simplex virus type 1 infection induces upregulation of interleukin-23 (p19) mRNA expression in trigeminal ganglia of BALB/c mice". J. Interferon Cytokine Res. 22 (6): 641–51. doi:10.1089/10799900260100123. PMID 12162874.
- Pirhonen J, Matikainen S, Julkunen I (2003). "Regulation of virus-induced IL-12 and IL-23 expression in human macrophages". J. Immunol. 169 (10): 5673–8. PMID 12421946.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Lo CH, Lee SC, Wu PY et al. (2003). "Antitumor and antimetastatic activity of IL-23". J. Immunol. 171 (2): 600–7. PMID 12847224.
- Clark HF, Gurney AL, Abaya E et al. (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=403697.
- Lee E, Trepicchio WL, Oestreicher JL et al. (2004). "Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris". J. Exp. Med. 199 (1): 125–30. doi:10.1084/jem.20030451. PMC 1887731. PMID 14707118. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1887731.
- Verreck FA, de Boer T, Langenberg DM et al. (2004). "Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria". Proc. Natl. Acad. Sci. U.S.A. 101 (13): 4560–5. doi:10.1073/pnas.0400983101. PMC 384786. PMID 15070757. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=384786.
- Smits HH, van Beelen AJ, Hessle C et al. (2004). "Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development". Eur. J. Immunol. 34 (5): 1371–80. doi:10.1002/eji.200324815. PMID 15114670.
- Schnurr M, Toy T, Shin A et al. (2005). "Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway". Blood 105 (4): 1582–9. doi:10.1182/blood-2004-05-1718. PMID 15486065.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
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IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21, IFNB1, IFNK, IFNW1
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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