AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch

Nat Immunol. 2011 Nov 20;13(2):144-51. doi: 10.1038/ni.2187.

Abstract

Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in ILC22 cells that resulted in less secretion of IL-22 and inadequate protection against intestinal bacterial infection. Ahr(-/-) mice also lacked postnatally 'imprinted' cryptopatches and isolated lymphoid follicles (ILFs), but not embryonically 'imprinted' Peyer's patches. AHR induced the transcription factor Notch, which was required for NKp46(+) ILCs, whereas LTi-like ILCs, cryptopatches and ILFs were partially dependent on Notch signaling. Thus, AHR was essential for ILC22 cells and postnatal intestinal lymphoid tissues. Moreover, ILC22 subsets were heterogeneous in their requirement for Notch and their effect on the generation of intestinal lymphoid tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Ly / metabolism
  • Female
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / metabolism
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Receptor, Notch1 / metabolism*
  • Receptor, Notch2 / metabolism*
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction / immunology

Substances

  • Antigens, Ly
  • Interleukins
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse
  • Notch1 protein, mouse
  • Notch2 protein, mouse
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptors, Aryl Hydrocarbon
  • interleukin-22