AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch
Top Cited Papers
- 20 November 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 13 (2), 144-151
- https://doi.org/10.1038/ni.2187
Abstract
The generation of certain gut innate lymphoid cell (ILC) populations requires the aryl hydrocarbon receptor (AHR). Colonna and colleagues show that the induction of Notch expression by AHR is required for the development of interleukin 22–producing NKp46+ ILCs. 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.Keywords
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