Papers of the Week

Atopic dermatitis (AD) is a highly prevalent, itchy inflammatory skin disorder that is thought to arise from a combination of defective skin barrier and immune dysregulation. Kallikreins (KLK), a family of serine proteases with a diverse array of homeostatic functions including skin desquamation and innate immunity, are speculated to contribute to AD pathogenesis. Their precise role in AD, however, has not been clearly defined. In this study, unbiased RNA-seq analyses identified KLK7 as the most abundant and differentially expressed KLK in both human AD and murine AD-like skin. Further, in mice, Klk7 expression was localized to the epidermis in both steady state and inflammation. However, KLK7 was dispensable for the development of AD-associated skin inflammation. Instead, KLK7 was selectively required for AD-associated chronic itch. Even without alleviation of skin inflammation, KLK7-deficient mice exhibited significantly attenuated scratching, compared to controls, after AD-like disease induction. Collectively, our findings indicate that KLK7 promotes AD-associated itch independently from skin inflammation, and reveal a previously unrecognized epidermal-neural mechanism of AD itch.