期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 48, 期 4, 页码 644-654出版社
WILEY
DOI: 10.1002/eji.201747102
关键词
Autoimmunity; CD161; Protein Kinase C epsilon; Psoriasis; Stat3
类别
资金
- Regione Emilia-Romagna Area 1 - Strategic Program
PKC epsilon is implicated in Tcell activation and proliferation and is overexpressed in CD4(+)-Tcells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKC epsilon takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKC epsilon expression in circulating CD4(+)-Tcells 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) PKC epsilon is overexpressed in CD4(+)-Tcells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKC epsilon interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKC epsilon is forcibly downregulated, CD4(+)-Tcells 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 PKC epsilon as a potential target in Th17-mediated diseases.
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