High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing γδ T cells

Sci Rep. 2017 Oct 26;7(1):14076. doi: 10.1038/s41598-017-14292-1.

Abstract

Psoriasis is a common, chronic inflammatory skin disease characterized by epidermal hyperplasia via the IL-23/IL-17 axis. Various studies have indicated the association between obesity and psoriasis, however, the underlying mechanisms remains unclarified. To this end, we focused on high-fat diet (HFD) in this study, because HFD is suggested as a contributor to obesity, and HFD-fed mice exhibit exacerbated psoriatic dermatitis. Using murine imiquimod (IMQ)-induced psoriasis and HFD-induced obesity models, we have revealed a novel mechanism of HFD-induced exacerbation of psoriatic dermatitis. HFD-fed mice exhibited aggravated psoriatic dermatitis, which was accompanied with increased accumulation of IL-17A-producing Vγ4+ γδ T cells in the skin. HFD also induced the increase of Vγ4+ γδ T cells in other organs such as skin draining lymph nodes, which preceded the increase of them in the skin. In addition, HFD-fed mice displayed increased expression of several γδ T cell-recruiting chemokines in the skin. On the other hand, ob/ob mice, another model of murine obesity on normal diet, did not exhibit aggravated psoriatic dermatitis nor accumulation of γδ T cells in the dermis. These results indicate that HFD is a key element in exacerbation of IMQ-induced psoriatic dermatitis, and further raise the possibility of HFD as a factor that links obesity and psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL20 / metabolism
  • Dermatitis / metabolism*
  • Dermatitis / pathology
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Imiquimod
  • Interleukin-17 / metabolism*
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / metabolism
  • Obesity / pathology
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • Skin / metabolism
  • Skin / pathology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology

Substances

  • CCL20 protein, mouse
  • Chemokine CCL20
  • Il17a protein, mouse
  • Interleukin-17
  • Imiquimod