Homeostatic Activation of Epidermal HSD11b1 Affects Skin Innervation and Non-Histaminergic Itch

The study investigated the role of epidermal HSD11b1 in non-histaminergic itch and skin innervation. Using wild type (WT) and K5 HSD11b1 knockout (cKO) mice, researchers found that cKO mice exhibited significantly more chloroquine (CQ)-induced scratching, but not histamine-induced scratching, compared to WT mice. Additionally, cKO mice showed reduced sensitivity to mechanical and thermal pain. Immunohistochemistry and 3D imaging revealed increased epidermal nerve sprouting and thicker nerve fibers around hair follicles in cKO mice. Despite no differences in TRP channels and MrgprA3 mRNA expression, cKO mice had elevated TSLP mRNA and protein levels in the epidermis. The findings suggested that TSLP from HSD11b1-null epidermis might influence skin innervation and enhance non-histaminergic itch.