PKCε promotes human Th17 differentiation: Implications in the pathophysiology of psoriasis.

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 duanyu1531ε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied duanyu1531ε 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) duanyu1531ε 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) duanyu1531ε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when duanyu1531ε 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 duanyu1531ε as a potential target in Th17-mediated diseases.

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