Interleukin 23 subunit alpha

Interleukin 23, alpha subunit p19
250px 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
File: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: 56.33 – 56.34 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. 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. A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.

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.

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.

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