Interleukin-23 (IL-23) plays a pivotal role in the intricate interplay between the skin, gut, and joints, contributing significantly to the pathogenesis of various inflammatory diseases including psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD) and Behcet's disease. In recent years, several IL-23 inhibitors have been granted approval for the treatment of psoriasis, PsA and IBD. As up to one-third of patients diagnosed with psoriasis may go on to develop PsA and given the strong immunogenetic pathway incrimination of the IL-23 pathway in both psoriasis and PsA, dermatological lead therapy for psoriasis may therefore delay the development of PsA. Furthermore, patients with psoriasis or PsA are associated with increased risk of developing IBD. There is also evidence for psoriasis-directed therapy preventing IBD in keeping with the known pivotal role of IL-23 in both intestinal homeostasis and in the pathogenesis of IBD, including ulcerative colitis and Crohn's disease. This review discusses the multifaceted roles of IL-23 in regulating immune response and maintaining tissue homeostasis within the skin-gut-joint axis. In particular, the use of IL-23 inhibitors in trials in patients with psoriasis, IBD and PsA patients will also be discussed in relation to reverse translational immunology insights around inflammation in these domains.
