Interleukin 23 subunit alpha

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

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). A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.

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.

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.

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

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. Risankizumab is another monoclonal antibody that targets IL-23A and is approved to treat plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.

Further reading

1. REDIRECT Template:Cytokines