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

By Jacob S. Lee, M. Cella, Keely G. McDonald, C. Garlanda, G. Kennedy, M. Nukaya, A. Mantovani, Raphael Kopan, Christopher A. Bradfield, R. Newberry and 1 more. Nature Immunology, 2011

773 citations recorded by the source corpus.

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.

Subfields: Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/a70acd67a85b383f7ffb947ad35c6e1d9c1e1e0e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Pathology and Forensic Medicine

Citations in the corpus

Intraepithelial type 1 innate lymphoid cells are a unique subset of cytokine responsive interferon-γ-producing cells (2013, neutral): “, 2013), AHR (Kiss et al., 2011; Lee et al., 2012; Qiu et al., 2012), and Notch (Lee et al.”
Interleukin-22: immunobiology and pathology (2015, background): “AhR is critical for ILC3-derived IL-22 production, either as a direct regulator of IL-22 gene expression or as a regulator of ILC3 and TH17 development (187, 190, 191).”
Innate Lymphoid Cells: 10 Years On. (2018, positive): “Consequently, an absence of AhR ligation impairs immunity to intestinal bacterial infections (Lee et al., 2011; Kiss et al., 2011).”
Mining the human gut microbiota for immunomodulatory organisms (2017, neutral): “Type 3 ILCs (ILC3s) were affected by only a few microbes, a result consistent with earlier studies reporting microbiota-mediated alterations in Il22 production, but not in overall ILC3 frequency (Lee et al., 2011; Reynders et al., 2011).”
The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “Additionally, independent studies have indicated that both the gut microbiota of patients with IBD and that of colitis-susceptible Card9−/− mice exhibit reductions in the concentration of tryptophan-derived indole derivatives that act as aryl hydrocarbon receptor ligands and promote IL-22 production”
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “For example, IL -22 produced by ILC3 promotes production and secretion of RegIII g, a secretory antimicrobial peptide by intestinal epithelial cells that has been shown to be critical in enteric infection by Citrobacter rodentium (99-101).”
Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. (2013, positive): “A substantial reduction in IL-22+NKp46+ pool size was observed in the gut upon depletion of lactobacilli, whereas monoassociation with L. reuteri increased IL-22 production by NKp46+ cells in GF mice, thus revealing that certain Lactobacillus species stimulate ILC3s for IL-22 production, an effect c”