Interleukin 23 subunit alpha

Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene.^[5][6] The protein is also known as IL-23p19. It is one of the two subunits of the cytokine Interleukin-23.

IL23A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3D85, 3D87, 3DUH, 3QWR, 4GRW, 4OE8, 4OG9
Identifiers
Aliases	IL23A, IL-23, IL-23A, IL23P19, P19, SGRF, Interleukin 23, interleukin 23 subunit alpha
External IDs	OMIM: 605580; MGI: 1932410; HomoloGene: 12832; GeneCards: IL23A; OMA:IL23A - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.3 Start 56,334,174 bp[1] End 56,340,410 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 D3 Start 128,132,008 bp[2] End 128,134,621 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle left testis right testis pancreatic ductal cell granulocyte sperm cartilage tissue gonad oocyte oral cavity Top expressed in secondary oocyte morula zygote primary oocyte decidua atrioventricular valve optic nerve cumulus cell endocardial cushion embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cytokine activity interleukin-23 receptor binding protein binding Cellular component interleukin-23 complex extracellular region extracellular space endoplasmic reticulum lumen Biological process negative regulation of interleukin-10 production positive regulation of inflammatory response positive regulation of interleukin-12 production positive regulation of interleukin-10 production immune system process positive regulation of T cell mediated cytotoxicity positive regulation of interferon-gamma production positive regulation of natural killer cell activation positive regulation of osteoclast differentiation positive regulation of T-helper 17 cell lineage commitment positive regulation of NK T cell activation T cell proliferation positive regulation of natural killer cell proliferation positive regulation of NK T cell proliferation positive regulation of T-helper 17 type immune response defense response to virus positive regulation of tissue remodeling positive regulation of T-helper 1 type immune response positive regulation of granulocyte macrophage colony-stimulating factor production defense response to Gram-negative bacterium positive regulation of T cell proliferation immune response positive regulation of memory T cell differentiation positive regulation of neutrophil chemotaxis positive regulation of tumor necrosis factor production positive regulation of interleukin-17 production innate immune response inflammatory response tissue remodeling positive regulation of transcription by RNA polymerase II positive regulation of activated T cell proliferation positive regulation of defense response to virus by host positive regulation of activation of Janus kinase activity regulation of tyrosine phosphorylation of STAT protein positive regulation of tyrosine phosphorylation of STAT protein regulation of signaling receptor activity cytokine-mediated signaling pathway interleukin-23-mediated signaling pathway positive regulation of NIK/NF-kappaB signaling Sources:Amigo / QuickGO
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: 128.13 – 128.13 Mb PubMed search [3] [4]
Wikidata
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Interleukin-23 (IL-23) is a heterodimeric cytokine composed of an Interleukin 23 alpha subunit and an IL-12p40 subunit. The IL-12p40, also known as Interleukin 12 subunit beta, is used by both IL-23 (where it partners with IL-23p19) and IL-12 (where it partners with IL-12A).^[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

Produced by dendritic cells and macrophages, 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.^[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]

Pharmacology

Several biologic drugs work by targeting IL-23A. Ustekinumab, a monoclonal antibody targeting both IL-12 and IL-23 and used to treat plaque psoriasis, psoriatic arthritis, and Crohn's disease, launched in the United States under the brand name Stelara.^[12] Risankizumab is another monoclonal antibody that targets IL-23A and is approved to treat plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.^[13][14][15]