Interleukin-21 receptor signalling is not critically required for imiquimod-induced psoriasiform dermatitis in mice

Exp Dermatol. 2018 Feb;27(2):191-195. doi: 10.1111/exd.13481. Epub 2018 Jan 5.

Abstract

Psoriasis is largely mediated by interleukin (IL)-23/T helper (Th) 17 axis, and IL-21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously reported possible pathogenic roles of IL-21 in human psoriasis, we found that IL-21 receptor (IL-21R) signalling was not crucial for imiquimod-induced psoriatic inflammation, using IL-21R-/- mice. The severity of imiquimod-induced psoriatic manifestation and pro-inflammatory Th17 cytokine levels, IL-17A-producing γδ T cells and CD4+ T cells, and in vitro IL-17A production by γδ T cells after IL-23 stimulation was comparable between wild-type and IL-21R-/- mice. Collectively, IL-21R signalling was not critically involved in IMQ-induced psoriatic inflammation despite an increased IL-21 expression in the IMQ-treated mouse skin. Our data may represent the significant differences between human psoriasis and murine psoriasis model, and further studies using other models will be required to elucidate the role of IL-21 in psoriasis pathogenesis.

Keywords: IL-17; IL-21 receptor knockout mouse; IL-22; IL-23; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • Dermatitis / genetics*
  • Dermatitis / metabolism
  • Imiquimod
  • Inflammation
  • Interferon Inducers / pharmacology
  • Interleukin-21 Receptor alpha Subunit / genetics
  • Interleukin-21 Receptor alpha Subunit / metabolism*
  • Interleukin-23 Subunit p19 / metabolism
  • Intraepithelial Lymphocytes / cytology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Psoriasis / chemically induced
  • Psoriasis / genetics*
  • Psoriasis / metabolism
  • Receptors, Interleukin-21 / genetics
  • Receptors, Interleukin-21 / metabolism*
  • Signal Transduction

Substances

  • Il21r protein, mouse
  • Il23a protein, mouse
  • Interferon Inducers
  • Interleukin-21 Receptor alpha Subunit
  • Interleukin-23 Subunit p19
  • Receptors, Interleukin-21
  • Imiquimod