Cited by 778IL-33, ST2, and ILC PathwaysT-cell and B-cell ImmunologyInflammatory Bowel Disease

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

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Lee, Jacob S, Cella, Marina, McDonald, Keely G, Garlanda, Cecilia, Kennedy, Gregory D, Nukaya, Manabu, Mantovani, Alberto, Kopan, Raphael +3 more·2012·Nature Immunology

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.

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  • Ahr−/− mice have multiple immunological deficits, including reduced resistance to Listeria monocytogenes, Citrobacter rodentium, and Candida albicans, exacerbated DSS-induced colitis, and altered susceptibility to EAE.

    “Ahr−/− mice suffer from multiple immunological deficits, including reduced resistance to infection with the bacteria Listeria monocytogenes or Citrobacter rodentium, as well as the fungus Candida albicans; exacerbated DSS-induced colitis; and even altered susceptibility to experimental autoimmune encephalomyelitis (EAE)”
  • AhR is required for postnatal maintenance of IL-22-producing ILC3s and for formation of isolated lymphoid follicles.

    “the AhR is in fact required for postnatal maintenance of IL-22-producing ILC3s, as well as the formation of isolated lymphoid follicles (Kiss et al., 2011; Lee et al., 2011; Y. Li et al., 2011; J. Qiu et al., 2012).”

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Authors
Lee, J. S., Cella, M., McDonald, K. G., Garlanda, C., Kennedy, G. D., Nukaya, M., Mantovani, A., Kopan, R., Bradfield, C. A., Newberry, R. D., & Colonna, M.
Affiliations
  • Washington University in St. Louis (US)
  • University of Wisconsin–Madison (US)
  • University of Milan (IT)
Corresponding author
Colonna, Marco
Venue
Nature Immunology
Published
2011-11-20
Volume
13
Issue
2
Pages
144-151
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2068162195
Cited by
777
References
50
Citations by year
2026: 27 · 2025: 36 · 2024: 57 · 2023: 40 · 2022: 51 · 2021: 61 · 2020: 54 · 2019: 61 · 2018: 59 · 2017: 60 · 2016: 59 · 2015: 58 · 2014: 58 · 2013: 61 · 2012: 34
FWCI
21.70
Type
journal article
Language
en
Open access
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Public Health Service (A1067854)
  • National Institute of General Medical Sciences (R01GM055479)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064798, P30DK020579, P30DK052574)
  • National Institute of Environmental Health Sciences (K08ES017283, R01ES005703)
  • National Institute of Dental and Craniofacial Research (R01DE021255)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
aryl hydrocarbon receptor, innate lymphoid cells, IL-22, Notch signaling, isolated lymphoid follicles, Peyer's patches, intestinal mucosal immunity, bacterial intestinal infections
MeSH terms
Interleukin-22, Animals, Antigens, Ly, Female, Interleukins, Lymphoid Tissue, Male, Mice, Inbred C57BL, Mice, Transgenic, Signal Transduction, Receptors, Aryl Hydrocarbon, Gastrointestinal Tract, Mice, Receptor, Notch1, Receptor, Notch2, Natural Cytotoxicity Triggering Receptor 1

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