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

Publication Type:

Featured

Source:

Nature immunology, Volume 13, Issue 2, p.144-51 (2012)

Keywords:

Animalsdigestive disease, digestive deseases Antigens, Lydigestive disease, digestive deseases Femaledigestive disease, digestive deseases Gastrointestinal Tractdigestive disease, digestive deseases Interleukinsdigestive disease, digestive deseases Lymphoid Tissuedigestive disease, digestive deseases Maledigestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, Inbred C57BLdigestive disease, digestive deseases Mice, Transgenicdigestive disease, digestive deseases Natural Cytotoxicity Triggering Receptor 1digestive disease, digestive deseases Receptor, Notch1digestive disease, digestive deseases Receptor, Notch2digestive disease, digestive deseases Receptors, Aryl Hydrocarbondigestive disease, digestive deseases Signal Transduction

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.