CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-induced model of psoriasiform dermatitis

J Invest Dermatol. 2013 Jan;133(1):164-71. doi: 10.1038/jid.2012.260. Epub 2012 Aug 16.

Abstract

A subset of CC chemokine receptor-6(+) (CCR6(+)), γδ-low (GDL) T cells that express Th17 cytokines in mouse skin participates in IL-23-induced psoriasiform dermatitis. We use CCR6-deficient (knockout, KO) and wild-type (WT) mice to analyze skin trafficking patterns of GDL T cells and function-blocking mAbs to determine the role of CCR6 in IL-23-mediated dermatitis. Herein, CCL20 was highly upregulated in IL-23-injected WT mouse ear skin as early as 24 hours after initial treatment, and large numbers of CCR6(+) cells were observed in the epidermis of IL-23-injected WT mice. Anti-CCL20 mAbs reduced psoriasiform dermatitis and blocked recruitment of GDL T cells to the epidermis. In CCR6 KO mice, GDL T cells failed to accumulate in the epidermis after IL-23 treatment, but the total numbers of GDL T cells in the dermis of WT and CCR6 KO mice were equivalent. There was an ∼70% reduction in the proportion of IL-22(+) GDL T cells in the dermis of CCR6 KO mice (vs WT mice), suggesting that effector function and epidermal recruitment of GDL T cells are impaired in CCR6-deficient mice. Thus, these data show that CCR6 regulates epidermal trafficking of γδ-T-cell subsets in the skin and suggest the potential of CCR6 as a therapeutic target for psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Chemokine CCL20 / immunology
  • Dermatitis / immunology*
  • Dermatitis / pathology
  • Epidermis / drug effects
  • Epidermis / immunology*
  • Epidermis / pathology
  • Interleukin-22
  • Interleukin-23 / adverse effects*
  • Interleukins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Psoriasis / chemically induced
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / drug effects
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / immunology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*

Substances

  • Antibodies, Blocking
  • CCL20 protein, mouse
  • CCR6 protein, mouse
  • Chemokine CCL20
  • Interleukin-23
  • Interleukins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR6