Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

Nat Commun. 2015 Jul 15;6:7687. doi: 10.1038/ncomms8687.

Abstract

Accumulating epidemiologic evidence has revealed that metabolic syndrome is an independent risk factor for psoriasis development and is associated with more severe psoriasis. Adiponectin, primarily recognized as a metabolic mediator of insulin sensitivity, has been newly drawing attention as a mediator of immune responses. Here we demonstrate that adiponectin regulates skin inflammation, especially IL-17-related psoriasiform dermatitis. Mice with adiponectin deficiency show severe psoriasiform skin inflammation with enhanced infiltration of IL-17-producing dermal Vγ4+γδ-T cells. Adiponectin directly acts on murine dermal γδ-T cells to suppress IL-17 synthesis via AdipoR1. We furthermore demonstrate here that the adiponectin level of skin tissue as well as subcutaneous fat is decreased in psoriasis patients. IL-17 production from human CD4- or CD8-positive T cells is also suppressed by adiponectin. Our data provide a regulatory role of adiponectin in skin inflammation, which would imply a mechanism underlying the relationship between psoriasis and metabolic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / immunology*
  • Adjuvants, Immunologic / toxicity
  • Adult
  • Aminoquinolines / toxicity
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Dermatitis / etiology
  • Dermatitis / immunology*
  • Female
  • Humans
  • Imiquimod
  • Immunoblotting
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-23 / toxicity
  • Male
  • Mice
  • Middle Aged
  • Psoriasis / immunology*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Adiponectin / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / immunology*
  • Subcutaneous Fat

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Adipoq protein, mouse
  • Adjuvants, Immunologic
  • Aminoquinolines
  • Interleukin-17
  • Interleukin-23
  • Receptors, Adiponectin
  • Receptors, Antigen, T-Cell, gamma-delta
  • adiponectin receptor 1, mouse
  • Imiquimod