IL23A

What is IL23A protein?

IL23A (interleukin 23 subunit alpha) gene is a protein coding gene which situated on the long arm of chromosome 12 at locus 12q13. This gene encodes a 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). The IL23A protein is consisted of 189 amino acids and its molecular mass is approximately 20.7 kDa.

What is the function of IL23A protein?

The IL23A protein binds to the IL12B protein to form the pro-inflammatory cytokine IL-23, a heterodimer factor that plays different roles in innate and adaptive immunity. IL-23 specifically acts on memory CD4(+) T cells, promoting the expansion and survival of helper T cells 17 (Th17), a CD4-positive subpopulation of helper T cells that produce IL-17. IL-23 plays a key role in the inflammatory process by promoting the production of pro-inflammatory cytokines such as interleukin 17A (IL17A), which in turn is involved in the regulation of inflammatory responses. Because of its role in a variety of inflammatory and autoimmune diseases, IL-23 has emerged as a potential drug target for the treatment of these conditions.

Fig1. Pathogenesis of IL-17-correlated disease and different targets of therapy. (Claudia Schinocca, 2021)

IL23A Related Signaling Pathway

When IL-23 binds to its receptor, it activates the JAK family of kinases, including JAK2 and TYK2, which in turn activates STAT3 and STAT4, leading to the activation of various signaling pathways, such as p38 MAPK or NF-κB. The IL-23 receptor consists of two subunits of the IL-12 receptor β1 (IL-12Rβ1) and the IL-23 receptor, a transmembrane protein whose extracellular region contains multiple functional domains. IL23A binds to IL12B to form the pro-inflammatory cytokine IL-23, a heterodimer factor that plays different roles in innate and adaptive immunity. IL-23 promotes the production of IL-17 by activating Th17 cells, which is involved in the amplification of inflammatory response and the regulation of autoimmune response.

IL23A Related Diseases

IL-23A is involved in the pathogenesis of psoriasis, especially in the activation of T cells and the inflammatory response in psoriasis. IL-23A is also involved in the inflammatory process of psoriatic arthritis, affecting pathological changes in the joints and skin. IL-23A plays a role in the pathogenesis of inflammatory bowel disease, specifically associated with Th17 cell activation and intestinal inflammatory response. The role of IL-23A in autoimmune diseases is receiving increasing attention because it plays a key role in regulating the immune response and promoting inflammation. IL-23A may be involved in the occurrence and development of a variety of other inflammatory diseases by affecting the activation of immune cells and the release of inflammatory mediators. IL-23A in the tumor microenvironment may promote tumor growth by affecting the activity of T cells and other immune cells.

Bioapplications of IL23A

IL23A is a potential target for drug development. Drugs have been developed that target IL23A or its receptors to treat diseases in which the IL23A signaling pathway is abnormal. IL23A acts as a cytokine and may be used to regulate immune responses, for example in immune deficiencies or autoimmune diseases. Studies have shown that IL23 cytokines can specifically act on activated CAR T cells and improve their proliferation after recognizing tumor antigens and anti-cancer function in multiple solid tumor models.