An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation

Nat Immunol. 2011 Oct 9;12(11):1071-7. doi: 10.1038/ni.2133.

Abstract

Interleukin 9 (IL-9) is a cytokine linked to lung inflammation, but its cellular origin and function remain unclear. Here we describe a reporter mouse strain designed to map the fate of cells that have activated IL-9. We found that during papain-induced lung inflammation, IL-9 production was largely restricted to innate lymphoid cells (ILCs). IL-9 production by ILCs depended on IL-2 from adaptive immune cells and was rapidly lost in favor of other cytokines, such as IL-13 and IL-5. Blockade of IL-9 production via neutralizing antibodies resulted in much lower expression of IL-13 and IL-5, which suggested that ILCs provide the missing link between the well-established functions of IL-9 in the regulation of type 2 helper T cell cytokines and responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / administration & dosage
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Genes, Reporter / genetics
  • Immunity, Innate
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology
  • Interleukin-9 / metabolism*
  • Lung
  • Lymphocyte Activation / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Lymphocytes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Papain / administration & dosage
  • Paracrine Communication
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*

Substances

  • Antibodies, Blocking
  • Cytokines
  • Interleukin-9
  • Papain