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Interleukin 23 subunit alpha

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IL23A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIL23A, IL-23, IL-23A, IL23P19, P19, SGRF, Interleukin 23, interleukin 23 subunit alpha
External IDsOMIM: 605580; MGI: 1932410; HomoloGene: 12832; GeneCards: IL23A; OMA:IL23A - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 10: 128.13 – 128.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene.[5][6] 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.[5] A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.[7]

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. Th17 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. Th17 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.[8]

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.[9][10]

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.[11]

Knockdown of AHR decreases the expression of IL23A in THP-1 cells and primary macrophage.[8]

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000110944 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025383 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. (November 2000). "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.
  6. ^ "Entrez Gene: IL23A interleukin 23, alpha subunit p19".
  7. ^ Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. (June 2002). "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.
  8. ^ a b Memari B, Bouttier M, Dimitrov V, Ouellette M, Behr MA, Fritz JH, White JH (November 2015). "Engagement of the Aryl Hydrocarbon Receptor in Mycobacterium tuberculosis-Infected Macrophages Has Pleiotropic Effects on Innate Immune Signaling". Journal of Immunology. 195 (9): 4479–91. doi:10.4049/jimmunol.1501141. PMID 26416282.
  9. ^ Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (July 2006). "IL-23 promotes tumour incidence and growth". Nature. 442 (7101): 461–5. doi:10.1038/nature04808. PMID 16688182. S2CID 4431794.
  10. ^ Kikly K, Liu L, Na S, Sedgwick JD (December 2006). "The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation". Current Opinion in Immunology. 18 (6): 670–5. doi:10.1016/j.coi.2006.09.008. PMID 17010592.
  11. ^ Korn T, Bettelli E, Oukka M, Kuchroo VK (2009). "IL-17 and Th17 Cells". Annual Review of Immunology. 27: 485–517. doi:10.1146/annurev.immunol.021908.132710. PMID 19132915.

Further reading

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