Rorγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice

J Clin Invest. 2012 Jun;122(6):2252-6. doi: 10.1172/JCI61862. Epub 2012 May 1.

Abstract

Psoriasis is a common, relapsing inflammatory skin disease characterized by erythematous scaly plaques. Histological manifestations of psoriasis include keratinocyte dysregulation and hyperproliferation, elongated rete ridges, and inflammatory infiltrates consisting of T cells, macrophages, dendritic cells, and neutrophils. Despite the availability of new effective drugs to treat psoriasis, the underlying mechanisms of pathogenesis are still poorly understood. Recent studies have shown that Aldara cream, used to treat benign skin abnormalities, triggers psoriasis-like disease in humans and mice and have implicated Th17 cells in disease initiation. Using this as a model, we found a predominant role for the Th17 signature cytokines IL-17A, IL-17F, and IL-22 in psoriasiform plaque formation in mice. Using gene-targeted mice, we observed that loss of Il17a, Il17f, or Il22 strongly reduced disease the severity of psoriasis. However, we found that Th17 cells were not the primary source of these pathogenic cytokines. Rather, IL-17A, IL-17F, and IL-22 were produced by a skin-invading population of γδ T cells and RORγt(+) innate lymphocytes. Furthermore, our findings establish that RORγt(+) innate lymphocytes and γδ T cells are necessary and sufficient for psoriatic plaque formation in an experimental disease model that closely resembles human psoriatic plaque formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Administration, Topical
  • Aminoquinolines / pharmacology
  • Animals
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Disease Models, Animal
  • Humans
  • Imiquimod
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukins / genetics
  • Interleukins / immunology
  • Macrophages / immunology
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology*
  • Psoriasis / drug therapy
  • Psoriasis / genetics
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Interleukin-17
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell, gamma-delta
  • Rorc protein, mouse
  • Imiquimod
  • interleukin-22