Interleukin 23 subunit alpha

Interleukin 23, alpha subunit p19
Rendering based on PDB 3D85​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3D85​, 3D87​, 3DUH​, 3QWR​, 4GRW​, 4OE8​, 4OG9​
Identifiers
Symbols	IL23A ; IL-23; IL-23A; IL23P19; P19; SGRF
External IDs	OMIM: 605580 MGI: 1932410 HomoloGene: 12832 GeneCards: IL23A Gene
Gene ontology Molecular function • cytokine activity • protein binding • interleukin-23 receptor binding Cellular component • interleukin-23 complex Biological process • positive regulation of T cell mediated cytotoxicity • positive regulation of defense response to virus by host • positive regulation of T-helper 1 type immune response • inflammatory response • positive regulation of activation of JAK2 kinase activity • negative regulation of interleukin-10 production • positive regulation of granulocyte macrophage colony-stimulating factor production • positive regulation of interferon-gamma production • positive regulation of interleukin-10 production • positive regulation of interleukin-12 production • positive regulation of interleukin-17 production • positive regulation of tumor necrosis factor production • positive regulation of natural killer cell activation • positive regulation of natural killer cell proliferation • positive regulation of tissue remodeling • T cell proliferation • positive regulation of T cell proliferation • positive regulation of activated T cell proliferation • positive regulation of NF-kappaB import into nucleus • regulation of tyrosine phosphorylation of Stat1 protein • positive regulation of tyrosine phosphorylation of Stat3 protein • positive regulation of tyrosine phosphorylation of Stat4 protein • positive regulation of tyrosine phosphorylation of Stat5 protein • positive regulation of memory T cell differentiation • innate immune response • positive regulation of osteoclast differentiation • positive regulation of transcription from RNA polymerase II promoter • tissue remodeling • positive regulation of inflammatory response • defense response to Gram-negative bacterium • positive regulation of NK T cell activation • positive regulation of NK T cell proliferation • defense response to virus • positive regulation of neutrophil chemotaxis • positive regulation of T-helper 17 type immune response • positive regulation of T-helper 17 cell lineage commitment Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	51561	83430
Ensembl	ENSG00000110944	ENSMUSG00000025383
UniProt	Q9NPF7	Q9EQ14
RefSeq (mRNA)	NM_016584	NM_031252
RefSeq (protein)	NP_057668	NP_112542
Location (UCSC)	Chr 12: 56.33 – 56.34 Mb	Chr 10: 128.3 – 128.3 Mb
PubMed search

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.

Interleukin-23 is a heterodimeric cytokine composed of an IL-12p40 subunit that is shared with IL-12 and the IL-23p19 subunit.^[1] A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.^[3]

Function

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 into tumours. IL-23 mediates its effects on both innate and adaptive arms of the immune system that express the IL-23 receptor. T_h17 cells represent the most prominent T cell subset that responds to IL-23, although IL-23 has been implicated in inhibiting the development of regulatory T cell development in the intestine. T_h17 cells produce IL-17, a proinflammatory cytokine that enhances T cell priming and stimulates the production of other proinflammatory molecules such as IL-1, IL-6, TNF-alpha, NOS-2, and chemokines resulting in inflammation. The expression of IL23A is decreased after AHR knockdown in THP-1 cells and primary mouse macrophages http://www.ncbi.nlm.nih.gov/pubmed/26416282

Clinical significance

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 experimental autoimmune encephalomyelitis (EAE) and inflammatory bowel disease highlighting the importance of IL-23 in the inflammatory pathway.^[4][5]

Discovery

A computational search for IL-12 homologue genes found p19, a gene that encodes a cytokine chain. Experimental work revealed that p19 formed a heterodimer by binding to p40, a subunit of IL-12. This new heterodimer was named IL-23.^[6]

See also

• Ustekinumab, a monoclonal antibody targeting both IL-12 and IL-23 and used to treat plaque psoriasis, launched in the United States under the brand name Stelara

References

1. 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.
2. "Entrez Gene: IL23A interleukin 23, alpha subunit p19".
3. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW (2000). "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R". Journal of Immunology 168 (11): 5699–708. doi:10.4049/jimmunol.168.11.5699. PMID 12023369.
4. 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.
5. 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.
6. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009). "IL-17 and Th17 Cells". Annu. Rev. Immunol. 27: 485–517. doi:10.1146/annurev.immunol.021908.132710. PMID 19132915.

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.
• Wiekowski MT, Leach MW, Evans EW, Sullivan L, Chen SC, Vassileva G, Bazan JF, Gorman DM, Kastelein RA, Narula S, Lira SA (2001). "Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death". J. Immunol. 166 (12): 7563–70. doi:10.4049/jimmunol.166.12.7563. PMID 11390512.
• Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW (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. doi:10.4049/jimmunol.168.11.5699. PMID 12023369.
• Broberg EK, Setälä N, Erälinna JP, Salmi AA, Röyttä M, Hukkanen V (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. doi:10.4049/jimmunol.169.10.5673. PMID 12421946.
• Lo CH, Lee SC, Wu PY, Pan WY, Su J, Cheng CW, Roffler SR, Chiang BL, Lee CN, Wu CW, Tao MH (2003). "Antitumor and antimetastatic activity of IL-23". J. Immunol. 171 (2): 600–7. PMID 12847224.
• Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F, Dhodapkar M, Krueger JG (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.
• Verreck FA, de Boer T, Langenberg DM, Hoeve MA, Kramer M, Vaisberg E, Kastelein R, Kolk A, de Waal-Malefyt R, Ottenhoff TH (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.
• Smits HH, van Beelen AJ, Hessle C, Westland R, de Jong E, Soeteman E, Wold A, Wierenga EA, Kapsenberg ML (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, Wagner M, Cebon J, Maraskovsky E (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.