189 Interleukin (IL)-26 drives pustular forms of psoriasis by linking neutrophils to keratinocyte activation

Abstract

Interleukin (IL-26) is an antimicrobial cytokine produced by Th17 cells and implicated in the pathogenesis of psoriasis. We found that the highest levels of IL-26 are present in pustular forms of psoriasis, released by neutrophils and not Th17 cells. In fact, neutrophils constitutively express IL-26 as a preformed protein, store it in primary granules, and release it upon microbial challenge. In pustular psoriasis, abundant levels of IL-26 are released by neutrophils sensing the commensal microbiota present in lower epidermal and dermal compartments of skin lesions. IL-26 then drives the pustular phenotype by activating keratinocytes to produce CXCL1, CXCL8 and IL-1a. Thus, our data identifies IL-26 as a key link between microbiota-activated neutrophils and keratinocytes leading to the development of pustular psoriasis