Regulation and function of interleukin‐36 cytokines

Summary The interleukin ( IL )‐36 cytokines include 3 agonists, IL ‐36α, IL ‐36β, and IL ‐36γ that bind to a common receptor composed of IL ‐36R and IL ‐1 RA cP to stimulate inflammatory responses. IL ‐36Ra is a natural antagonist that binds to IL ‐36R, but does not recruit the co‐receptor IL ‐1 RA cP and does not stimulate any intracellular responses. The IL ‐36 cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells, and fibroblasts. Processing of the N‐terminus is required for full agonist or antagonist activity for all IL ‐36 members. The role of IL ‐36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response that has been implicated in psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary and intestinal physiology and pathology.