Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation

Abstract

Mechanical damage on the skin not only affects barrier function but also induces various immune responses, which trigger or exacerbate skin inflammation. However, how mechanical damage-induced skin inflammation is regulated remains incompletely understood. Here, we show that keratinocytes express the long-chain fatty-acid elongase Elovl6. Mice deficient in Elovl6 showed higher levels of cis-vaccenic acid (CVA) in the epidermis and severe skin inflammation induced by mechanical damage due to tape stripping than did wild-type mice. CVA accelerated tape stripping-triggered keratinocyte death and release of danger-associated molecular patterns (DAMPs) such as high-mobility group box 1 protein (HMGB-1) and IL-1α, which induced production of proinflammatory cytokines and chemokines IL-1β and CXCL-1 by keratinocytes. Our results demonstrate that Elovl6 regulates mechanical damage—triggered keratinocyte death and the subsequent dermatitis.