Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis

Mucosal Immunol. 2016 Jan;9(1):275-86. doi: 10.1038/mi.2015.59. Epub 2015 Jul 1.

Abstract

Group 2 innate lymphoid cells (ILC2s) have an important role in acute allergic lung inflammation. Given their distribution and function, lung ILC2s are hypothesized to coordinate epithelial responses to the external environment; however, how barrier surveillance is linked to ILC2 activation remains unclear. Here, we demonstrate that alveolar type II cells are the main source of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) generated in response to chitin or migratory helminths. IL-33 and TSLP synergistically induce an interferon regulatory factor 4 (IRF4)-IL-9 program in ILC2s, and autocrine IL-9 promotes rapid IL-5 and IL-13 production required for optimal epithelial responses in the conducting airways. Thus, ILC2s link alveolar function to regulation of airway flow, revealing a key interaction between resident lymphoid and structural cells that might underlie similar organizational hierarchies in other organs.

Publication types

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

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Chitin
  • Cytokines / genetics
  • Cytokines / immunology
  • Epithelial Cells / immunology*
  • Epithelial Cells / parasitology
  • Gene Expression Regulation
  • Immunity, Innate
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-33 / genetics
  • Interleukin-33 / immunology
  • Interleukin-5 / genetics
  • Interleukin-5 / immunology
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology*
  • Lung / immunology
  • Lung / parasitology
  • Lymphocytes / immunology*
  • Lymphocytes / parasitology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nippostrongylus / immunology
  • Nippostrongylus / parasitology
  • Pneumonia / chemically induced
  • Pneumonia / genetics
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Primary Cell Culture
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / parasitology
  • Signal Transduction
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • Strongylida Infections / pathology

Substances

  • Cytokines
  • Il33 protein, mouse
  • Interferon Regulatory Factors
  • Interleukin-13
  • Interleukin-33
  • Interleukin-5
  • Interleukin-9
  • interferon regulatory factor-4
  • Chitin
  • thymic stromal lymphopoietin