Cutaneous Immunosurveillance and Regulation of Inflammation by Group 2 Innate Lymphoid Cells

Nat Immunol. 2013 Jun;14(6):564-73. doi: 10.1038/ni.2584. Epub 2013 Apr 21.

Abstract

Type 2 immunity is critical for defense against cutaneous infections but also underlies the development of allergic skin diseases. We report the identification in normal mouse dermis of an abundant, phenotypically unique group 2 innate lymphoid cell (ILC2) subset that depended on interleukin 7 (IL-7) and constitutively produced IL-13. Intravital multiphoton microscopy showed that dermal ILC2 cells specifically interacted with mast cells, whose function was suppressed by IL-13. Treatment of mice deficient in recombination-activating gene 1 (Rag1(-/-)) with IL-2 resulted in the population expansion of activated, IL-5-producing dermal ILC2 cells, which led to spontaneous dermatitis characterized by eosinophil infiltrates and activated mast cells. Our data show that ILC2 cells have both pro- and anti-inflammatory properties and identify a previously unknown interactive pathway between two innate populations of cells of the immune system linked to type 2 immunity and allergic diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / immunology
  • Cells, Cultured
  • Dermatitis / genetics
  • Dermatitis / immunology*
  • Dermatitis / metabolism
  • Dermis / cytology
  • Dermis / immunology
  • Dermis / metabolism
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Flow Cytometry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Homeodomain Proteins / metabolism
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton
  • Skin / immunology*
  • Skin / metabolism
  • Videotape Recording

Substances

  • Homeodomain Proteins
  • Interleukin-13
  • Interleukin-17
  • Interleukin-2
  • RAG-1 protein
  • Green Fluorescent Proteins