IL23

Interleukin-23 (IL-23) is a heterodimeric proinflammatory cytokine in the interleukin-12 (IL-12) family. It is composed of a p19 subunit paired with a p40 subunit, the latter of which is shared with IL-12. IL-23 is produced mainly by antigen-presenting cells such as dendritic cells and macrophages in response to microbial stimuli, and it plays a key role in shaping and sustaining inflammatory T cell responses.

IL-23 signals through the IL-23 receptor, which consists of IL-23R and IL-12Rβ1. The signaling cascade engages JAK2 and TYK2, predominantly activating the transcription factor STAT3. Through this pathway, IL-23 promotes the survival, expansion, and effector function of Th17 cells and also enhances the activity of innate lymphoid cells (ILC3) and gamma-delta T cells, contributing to a broader Th17-mediated immune response.

Functionally, IL-23 supports host defense against certain extracellular bacteria and fungi by reinforcing proinflammatory cytokine production. However, when dysregulated, IL-23–driven Th17 responses can contribute to chronic tissue inflammation and autoimmune pathology, particularly at mucosal and skin sites.

Clinical relevance and therapeutics: Abnormal IL-23 signaling is associated with diseases such as psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Therapeutic agents target the IL-23 axis either by inhibiting the p19 subunit (guselkumab, risankizumab, tildrakizumab) to selectively block IL-23, or by targeting the p40 subunit (ustekinumab) to block both IL-23 and IL-12. These strategies aim to reduce pathogenic Th17-driven inflammation while preserving broader immune function.