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any of several lymphokines that promote macrophages and killer T cells and B cells and other components of the immune system

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/08 17:25:51」(JST)

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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]

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.
^ "Entrez Gene: IL23A interleukin 23, alpha subunit p19".
^ 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.
^ 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.
^ 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.

UpToDate Contents

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English Journal

Interleukin-23: A key cytokine in inflammatory diseases.

Duvallet E, Semerano L, Assier E, Falgarone G, Boissier MC.SourceSorbonne Paris Cite Universite Paris 13 EA4222 74, rue Marcel Cachin 93000 Bobigny France, Assistance Publique - Hopitaux de Paris (AP-HP) Groupe hospitalier Avicenne - Jean Verdier - Rene Muret , Service de Rhumatologie 125, rue de Stalingrad 93000 Bobigny France.
Annals of medicine.Ann Med.2011 Nov;43(7):503-11. Epub 2011 May 17.
Abstract Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of two subunits, p19 and p40. The p40 subunit is shared with IL-12. IL-23 and IL-12 have different receptors and different effects. Whereas IL-12 induces development of Th1 cells, which produce interferon-γ, IL-23 is involved i
PMID 21585245

The IL-23 axis in Salmonella gastroenteritis.

Godinez I, Keestra AM, Spees A, Baumler AJ.SourceDepartment of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA, USA.
Cellular microbiology.Cell Microbiol.2011 Nov;13(11):1639-47. doi: 10.1111/j.1462-5822.2011.01637.x. Epub 2011 Jul 11.
Non-typhoidal Salmonella (NTS) serotypes cause a localized gastroenteritis in immunocompetent individuals. In contrast, primary immunodeficiencies that impair interleukin-23 (IL-23)-dependent pathways are associated in humans with disseminated NTS bloodstream infections (bacteraemia). The recent use
PMID 21740501

Japanese Journal

生物学的製剤による乾癬の治療

多田弥生,佐藤伸一
日本臨床免疫学会会誌 = Japanese journal of clinical immunology 33(3), 126-134, 2010-06-30
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NAID 10026543204

Positive treatment effects of ustekinumab in psoriasis : Analysis of lesional and systemic parameters

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Journal of dermatology 37(5), 413-425, 2010-05-01
NAID 10026432950

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拡張検索	「interleukin-23 subunit p19」
関連記事	「interleukin」「interleukins」

「interleukin-23 subunit p19」

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
	v; t; e;