The IL-17A-producing CD8+ T-cell population in psoriatic lesional skin comprises mucosa-associated invariant T cells and conventional T cells

J Invest Dermatol. 2014 Dec;134(12):2898-2907. doi: 10.1038/jid.2014.261. Epub 2014 Jun 18.

Abstract

IL-17A is pivotal in the etiology of psoriasis, and CD8(+) T cells with the ability to produce this cytokine (Tc17 cells) are over-represented in psoriatic lesions. Here we demonstrate that the frequency of Tc17 cells in peripheral blood of psoriasis patients correlated with the clinical severity of the disease. Analysis of cutaneous-associated lymphocyte antigen expression showed that the blood Tc17 population contains a significantly higher proportion of cells with skin-homing potential compared with the CD8(+) T-cell population lacking IL-17A/IL-22 expression. IL-17A-producing CD8(+) T cells in blood have previously been reported to belong mainly to the mucosa-associated invariant T-cell (MAIT cell) lineage characterized by TCR Vα7.2 chain, CD161, IL-18Rα, and multidrug transporter ABCB1 expression. We demonstrate the presence of CD8(+) MAIT cells in the dermis and epidermis of psoriatic plaques, as well as healthy skin; however, IL-17A-producing CD8(+) MAIT cells were predominantly found in psoriatic skin. Notably, we observed IL-17A production in a large proportion of psoriatic plaque-derived CD8(+) T cells devoid of MAIT cell characteristics, likely representing conventional CD8(+) T cells. In conclusion, we provide supporting evidence that implicates Tc17 cells in the pathogenesis of psoriasis and describe the presence of innate CD8(+) MAIT cells in psoriatic lesions as an alternative source of IL-17A.

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology*
  • Case-Control Studies
  • Cell Count
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism*
  • Interleukins / metabolism
  • Male
  • Middle Aged
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Psoriasis / metabolism
  • Psoriasis / pathology*
  • Retrospective Studies
  • Severity of Illness Index
  • Skin / metabolism
  • Skin / pathology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*

Substances

  • Interleukin-17
  • Interleukins
  • Interferon-gamma
  • interleukin-22