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

Eur J Immunol. 2018 Apr;48(4):644-654. doi: 10.1002/eji.201747102. Epub 2018 Feb 5.

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.

Keywords: Autoimmunity; CD161; Protein Kinase C epsilon; Psoriasis; Stat3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoimmunity / immunology
  • Cell Differentiation / immunology*
  • Cell Polarity / immunology
  • Cells, Cultured
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Protein Kinase C-epsilon / metabolism*
  • Psoriasis / immunology
  • Psoriasis / physiopathology*
  • STAT3 Transcription Factor / metabolism
  • Th17 Cells / cytology*
  • Th17 Cells / immunology*

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Protein Kinase C-epsilon