The role of IL‐23 and the IL‐23/T_H17 immune axis in the pathogenesis and treatment of psoriasis

Abstract

Psoriasis is a chronic, immune‐mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL‐23)/T‐helper 17 (TH17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis. Central to this pathway is the cytokine IL‐23, a heterodimer composed of a p40 subunit also found in IL‐12 and a p19 subunit exclusive to IL‐23. IL‐23 is important for maintaining TH17 responses, and levels of IL‐23 are elevated in psoriatic skin compared with non‐lesional skin. A number of agents that specifically inhibit IL‐23p19 are currently in development for the treatment of moderate‐to‐severe plaque psoriasis, with recent clinical trials demonstrating efficacy with a good safety and tolerability profile. These data support the role of this cytokine in the pathogenesis of psoriasis. A better understanding of the IL‐23/TH17 immune axis is vital and will promote the development of additional targets for psoriasis and other inflammatory diseases that share similar genetic aetiology and pathogenetic pathways.

Efficacy and safety of risankizumab in Japanese patients with moderate to severe plaque psoriasis: Results from the SustaIMM phase 2/3 trial

“…Interleukin‐23 is a key cytokine in the pathogenesis of psoriasis . Produced by dendritic cells and macrophages, IL‐23 is a heterodimer composed of a unique p19 subunit and an associated p40 subunit shared with IL‐12 .…”

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

“…Psoriasis is a chronic T‐cell‐mediated inflammatory skin disease, estimated to affect more than 100 million individuals worldwide, of whom approximately 20% have moderate to severe disease . The pathogenesis of psoriasis is complex; however, there is robust evidence that the interleukin (IL)‐23/IL‐17 immune axis is a key driver of psoriatic inflammation . Over the past 2 decades, biologic treatment of moderate to severe psoriasis has changed the disease management paradigm.…”

“…Several agents targeting the IL‐23 cytokine pathway are now available. IL‐23 is a heterodimer composed of two subunits: p40, which is shared with IL‐12, and p19 . Data from long‐term clinical trials and a large safety registry (Psoriasis Longitudinal Assessment and Registry; PSOLAR) have shown the IL‐12/23p40 inhibitor ustekinumab to be well tolerated in patients with psoriasis .…”

Gold lotion from citrus peel extract ameliorates imiquimod‐induced psoriasis‐like dermatitis in murine

“…Early studies suggested that psoriasis is a chronic‐relapsing T‐helper (Th)1‐type disease based on the elevated levels of IFN‐γ, TNF‐α, and IL‐12 that are observed. Subsequently, a functional role of IL‐23/Th17 in the immunopathogenesis of psoriasis was demonstrated . Th17 cells are inflammatory Th cells characterized by the expression of IL‐17A/F, IL‐21, IL‐22, and potentially TNF‐α and IL‐6, and a high level of retinoic acid‐related orphan receptors (RORα and RORγ) .…”