Role of IL-36 cytokines in psoriasis and other inflammatory skin conditions

The IL-36 family of cytokines includes three pro-inflammatory agonists (IL-36 alpha, IL-368, and IL-36 gamma) and a receptor antagonist (IL-36Ra), which bind and signal through a heterodimeric receptor composed of IL-36R and the IL-1R accessory protein (IL-1RAcP). Individuals with inactivating mutations in the gene encoding IL-36Ra develop generalized pustular psoriasis, a severe form of psoriasis, a finding which clearly links dysregulated IL-36 pathway activation to inflammatory skin conditions. The purpose of this review is to highlight the cellular source of IL-36 cytokines, the effects of IL-36 signaling across cell types, and the association of IL-36 to a spectrum of inflammatory skin diseases including various forms of psoriasis as well as hidradenitis suppurativa, atopic dermatitis, and allergic contact dermatitis.