Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

Nat Immunol. 2011 Nov;12(11):1045-54. doi: 10.1031/ni.2131.

Abstract

Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor a-chain (CD25), IL-7 receptor a-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.

Publication types

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

MeSH terms

  • Airway Remodeling / drug effects
  • Airway Remodeling / immunology
  • Amphiregulin
  • Animals
  • Antigens, CD / biosynthesis
  • Cells, Cultured
  • EGF Family of Proteins
  • Glycoproteins / pharmacology
  • Homeostasis* / immunology
  • Humans
  • Immunity, Innate*
  • Influenza, Human / immunology*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Interleukin-33
  • Interleukins / metabolism
  • Lung / immunology
  • Lung / metabolism*
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae / immunology*
  • Orthomyxoviridae Infections / immunology*
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / virology
  • Wound Healing

Substances

  • AREG protein, human
  • Amphiregulin
  • Antigens, CD
  • Areg protein, mouse
  • EGF Family of Proteins
  • Glycoproteins
  • Il33 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-33
  • Interleukins