Interleukin 23 subunit alpha

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Interleukin 23, alpha subunit p19

Rendering based on PDB 3D85.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols IL23A ; IL-23; IL-23A; IL23P19; P19; SGRF
External IDs OMIM605580 MGI1932410 HomoloGene12832 GeneCards: IL23A Gene
RNA expression pattern
PBB GE IL23A 220054 at tn.png
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:
56.73 – 56.73 Mb
Chr 10:
128.3 – 128.3 Mb
PubMed search [1] [2]

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.

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: p40, which is also a component of the IL-12 cytokine, p19, which is considered 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. 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 cells and Th2 cells cells. 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.

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[edit]

Interleukin 23 has been shown to interact with Interleukin-12 subunit beta.[1]

Discovery[edit]

A computational search for IL-6 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-6. This new heterodimer was named IL-23.[5]

See also[edit]

  • 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[edit]

  1. ^ 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. 
  2. ^ a b "Entrez Gene: IL23A interleukin 23, alpha subunit p19". 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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[edit]