Current and Emerging Therapies Targeting the IL-23/IL-17 Axis in Psoriasis.

Abstract

Over the past two decades, experimental and clinical evidence has established the interleukin-23 (IL-23)/interleukin-17 (IL-17) axis as a key mediator of psoriatic inflammation. IL-23, primarily derived from activated dendritic cells, supports the survival and pathogenic function of type 17 immune cells, which subsequently release IL-17A, IL-17F, and IL-22 to promote keratinocyte activation and recruit inflammatory leukocytes. These mechanistic insights have directly translated into the development of highly effective biologic therapies targeting IL-17 or IL-23, substantially improving the management of psoriasis. Beyond injectable biologics, growing efforts to overcome limitations related to long-term adherence, cost, and accessibility have accelerated the development of non-injectable therapeutic approaches. Oral and topical small-molecule agents, including selective tyrosine kinase 2 (TYK2) inhibitors and IL-23 receptor antagonists, are now broadening the therapeutic options. At the same time, progress in molecular engineering, artificial intelligence-guided protein design, and spatial multi-omic technologies are refining therapeutic discovery and enabling more precise targeting of pathogenic immune circuits. In this review, we outline the current understanding of the IL-23/IL-17 pathway in psoriasis pathogenesis and provide a critical overview of approved and emerging therapies directed at this pathway. We also address key biological and translational challenges, including tissue-specific cytokine functions, interspecies differences, and long-term safety considerations, and discuss how these factors may inform future strategies for precision immunotherapy in psoriasis.