Systemically dispersed innate IL-13-expressing cells in type 2 immunity

Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11489-94. doi: 10.1073/pnas.1003988107. Epub 2010 Jun 7.

Abstract

Type 2 immunity is a stereotyped host response to allergens and parasitic helminths that is sustained in large part by the cytokines IL-4 and IL-13. Recent advances have called attention to the contributions by innate cells in initiating adaptive immunity, including a novel lineage-negative population of cells that secretes IL-13 and IL-5 in response to the epithelial cytokines IL-25 and IL-33. Here, we use IL-4 and IL-13 reporter mice to track lineage-negative innate cells that arise during type 2 immunity or in response to IL-25 and IL-33 in vivo. Unexpectedly, lineage-negative IL-25 (and IL-33) responsive cells are widely distributed in tissues of the mouse and are particularly prevalent in mesenteric lymph nodes, spleen, and liver. These cells expand robustly in response to exogenous IL-25 or IL-33 and after infection with the helminth Nippostrongylus brasiliensis, and they are the major innate IL-13-expressing cells under these conditions. Activation of these cells using IL-25 is sufficient for worm clearance, even in the absence of adaptive immunity. Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses.

Publication types

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

MeSH terms

  • Animals
  • Cell Lineage
  • Cytokines / metabolism
  • Eosinophils / parasitology
  • Immune System
  • Immunity, Innate
  • Interleukin-13 / chemistry*
  • Interleukin-13 / metabolism
  • Interleukin-33
  • Interleukin-4 / metabolism
  • Interleukins / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nippostrongylus / metabolism
  • Nippostrongylus / pathogenicity*

Substances

  • Cytokines
  • Il33 protein, mouse
  • Interleukin-13
  • Interleukin-33
  • Interleukins
  • Mydgf protein, mouse
  • Interleukin-4