Granzyme A potentiates chemokine production in IL-17-stimulated keratinocytes

Exp Dermatol. 2017 Sep;26(9):824-827. doi: 10.1111/exd.13284. Epub 2017 Apr 10.

Abstract

Plaque psoriasis presents with focal skin inflammation, partially maintained by IL-17-mediated interactions between infiltrating epidermal T cells and activated keratinocytes. Here we show that the majority of lesional epidermal CD8 T cells express granzyme A, alone or in combination with IL-17. To assess proinflammatory properties of granzyme A in psoriasis, primary human keratinocytes were stimulated with granzyme A in the presence or absence of IL-17. Out of 33 analysed keratinocyte-derived inflammatory mediators, granzyme A potentiated IL-17-induced secretion of CXCL 1, CXCL 12 and CCL 4. Intriguingly, all three chemokines are implicated in psoriasis pathogenesis and are involved in recruitment of T cells, neutrophils and pDCs into inflamed tissues. Our results indicate that granzyme A produced by lesional CD8 T cells specifically increase the chemokine production from inflamed keratinocytes, thereby amplifying a chemotactic inflammatory loop that sustains psoriasis lesions.

Keywords: T cells; cytotoxic granules; inflammation; psoriasis; serine proteases.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / enzymology*
  • Case-Control Studies
  • Female
  • Granzymes / metabolism*
  • Humans
  • Interleukin-17 / metabolism*
  • Keratinocytes / metabolism*
  • Male
  • Middle Aged
  • Psoriasis / enzymology
  • Psoriasis / immunology*

Substances

  • Interleukin-17
  • Granzymes