032 IL-36 axis is a sex-biased immune amplification circuit localized to the supraspinous epidermal compartment

Abstract

Both psoriasis and pustular psoriasis are characterized by prominent involvement of IL-36 family of cytokines, which consists of three pro-inflammatory cytokines: IL-36A, IL-36B and IL-36G, and the IL-36 receptor antagonist (IL-36RA/IL36RN). IL-36 cytokines are significantly increased in psoriatic skin, and on average about 5-10-fold elevated in pustular forms of psoriasis. Using single-cell and spatial-seq approaches we have demonstrated that IL-36 responses are primarily localized to the supraspinous compartment of the epidermis, and strongly correlate with, and act downstream of, both IL-17A and TNF responses.