Interleukin23

Interleukin-23 (IL-23) is a cytokine in the interleukin-12 (IL-12) family that functions as a heterodimer composed of the p19 and p40 subunits. The p40 subunit is shared with IL-12, which distinguishes IL-23 from IL-12 in its composition and signaling.

IL-23 is produced mainly by activated dendritic cells and macrophages in response to microbial products and other inflammatory stimuli. It acts on cells expressing the IL-23 receptor, a heterodimer of IL-23R and IL-12Rβ1, including T cells, natural killer cells, and group 3 innate lymphoid cells. Signaling through this receptor activates the JAK-STAT pathway, primarily engaging STAT3, and promotes the expansion and maintenance of Th17 cells, enhancing the production of IL-17A, IL-17F, and other pro-inflammatory mediators. IL-23 is more involved in sustaining an ongoing Th17 response rather than the initial differentiation of naive T cells into Th17 cells, which requires additional signals such as IL-6 and TGF-β.

IL-23 plays a significant role in mucosal and systemic inflammation and has been implicated in autoimmune diseases such as psoriasis, inflammatory bowel disease, psoriatic arthritis, and ankylosing spondylitis. Therapeutically, its pathway can be targeted with monoclonal antibodies. Anti-p19 antibodies (guselkumab, tildrakizumab, risankizumab) selectively block IL-23, while anti-p40 antibodies (ustekinumab) inhibit both IL-23 and IL-12.

Beyond pathology, IL-23 contributes to host defense by activating Th17 cells and innate lymphoid cells, particularly at mucosal sites, where balanced signaling is important for antimicrobial responses and tissue homeostasis.