PKCε promotes human Th17 differentiation: implications in the pathophysiology of Psoriasis

Abstract

PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4⁺-T cells from patients with autoimmune Hashimoto's Thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4⁺-T cells from patients with Psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4⁺ subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: i)PKCε is overexpressed in CD4⁺-T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; ii)PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4⁺-T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases.

This article is protected by copyright. All rights reserved

http://ift.tt/2pGRLPD