IL23A

IL23A Full Name

Interleukin 23, alpha subunit p19

IL23A Introduction

IL23A is the human gene which encodes the interleukin-23 (IL-23) alpha subunit (p19), one of the two chains which comprise the heterodimeric cytokine IL-23. The two chains are linked by a covalent disulfide bond. The cytokine subunit that pairs with p19 in the cytokine IL-23 is a p40 subunit (encoded by the IL12B gene), which is also used in the structurally related cytokine IL-12. The free p19 subunit has little biological activity when tested in vitro. The main molecular function of the p19 subunit is binding to p40 to make the functional cytokine IL-23. Expression of the p19 subunit is tightly controlled and the subunit is produced mainly by activated antigen-presenting cells, including dendritic cells and macrophages.

By virtue of forming IL-23, IL23A performs a prototypic pro-inflammatory function in immunity by promoting the differentiation, maintenance and effector functions of Th17 cells. Secreted functional IL-23 (p19/p40) engages with the IL-23 receptor complex (R) on target cell surfaces. The IL-23 receptor is a heterodimer composed of the IL-23R subunit and the IL-12Rβ1 subunit (the shared component of IL-12R). The receptor complex, in turn, signals to the intracellular JAK-STAT pathway primarily via phosphorylation and activation of JAK2 and TYK2 kinases. These events lead to the activation of signal transducer and activator of transcription 3 (STAT3). Activated STAT3 enters the nucleus and modulates the transcription of numerous target genes critical for the survival, proliferation and effector functions of Th17 cells. Th17 cells are powerful pro-inflammatory effector cells that can produce several cytokines, including IL-17A, IL-17F, and IL-22. These cytokines are central to host defense (particularly against extracellular bacteria and fungi) but also drive tissue inflammation and autoimmunity. Thus, as the key component of IL-23, IL23A functions as the "initiator" of the entire IL-23/Th17 immune axis and thus has a critical impact on the downstream inflammatory pathways.

Dysregulation and overactivation of IL-23/Th17 axis have been reported to be implicated in the pathogenesis of various diseases, such as psoriasis, inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) and ankylosing spondylitis. In addition, genetic studies have shown strong associations of the polymorphisms in IL-23-related genes (particularly IL-23 receptor gene, IL23R) with disease susceptibility in these diseases, further supporting the pathological importance of this pathway. Following the insight, inhibitors targeting the IL-23 p19 subunit were developed as the novel therapeutic strategies. With this design, the biologics can specifically block the biological activity of IL-23 but not that of IL-12 (which also shares the p40 subunit with IL-23), thus allowing more specific immune modulation.

Figure 1. Schematic representation of IL-23–producing cells and IL-23 target cells implicated in PsO, PsA, and IBD pathogenesis. (Source: Krueger JG, et al. 2024)

Alternate Names for IL23A

IL23A; interleukin 23; alpha subunit p19; P19; SGRF; IL-23; IL-23A; IL23P19; interleukin-23 subunit alpha; IL-23-A; IL-23p19; IL-23 subunit alpha; interleukin 23 p19 subunit; interleukin-23 subunit p19; JKA3 induced upon T-cell activation; interleukin-six; G-CSF related factor; BI 655066

• 1. Langrish CL, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005 Jan 17;201(2):233-40.
  2. Krueger JG, et al. IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol. 2024 Apr 15;15:1331217.