The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“This idea has been supported and expanded upon recently as additional evidence emerges detailing missing or impaired populations of resident immune cells in adult null mice at barrier tissues like the lung, intestine, and skin (Esser & Rannug, 2015; Kiss et al., 2011; Lee et al., 2012; Li et al., 2018; Qiu et al., 2012; Stockinger et al., 2014).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lee et al., 2012
In the citing paper
“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)”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Lee et al., 2011
In the citing paper
“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).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Lee et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
Zheng, Y., Valdez, P. A., Danilenko, D. M., Hu, Y., Susan, M. L., Gong, Q., Abbas, A. R., Modrusan, Z. D., Ghilardi, N., de Sauvage, F. J., et al. (2008) · Nature Medicine · doi:10.1038/nm1720 · Cited by 1,972
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011) · Nature · doi:10.1038/nature10491 · Cited by 1,898
Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor
Quintana, F. J., Basso, A. S., Iglesias, A. H., Korn, T., Farez, M. F., Bettelli, E., Caccamo, M., Oukka, M., & Weiner, H. L. (2008) · Nature · doi:10.1038/nature06880 · Cited by 1,865
The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation
Ouyang, W., Kolls, J. K., & Zheng, Y. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.004 · Cited by 1,750
An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells
Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J., & Bradfield, C. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903670 · Cited by 1,674
Self-citationThe aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
Veldhoen, M., Hirota, K., Westendorf, A. M., Buer, J., Dumoutier, L., Renauld, J.-C., & Stockinger, B. (2008) · Nature · doi:10.1038/nature06881 · Cited by 1,634
Immune adaptations that maintain homeostasis with the intestinal microbiota
Hooper, L. V., & Macpherson, A. J. (2010) · Nature reviews. Immunology · doi:10.1038/nri2710 · Cited by 1,530
A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity
Cella, M., Fuchs, A. G., Vermi, W., Facchetti, F., Otero, K., Lennerz, J. K., Doherty, J. M., Mills, J. C., & Colonna, M. (2008) · Nature · doi:10.1038/nature07537 · Cited by 1,298
Self-citationSatoh‐Takayama, N., Vosshenrich, C. A. J., Lesjean‐Pottier, S., Sawa, S., Lochner, M., Rattis, F. M., Mention, J., Thiam, K., Cerf–Bensussan, N., Mandelboim, O., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.11.001 · Cited by 1,133
Sonnenberg, G. F., Fouser, L. A., & Artis, D. (2011) · Nature Immunology · doi:10.1038/ni.2025 · Cited by 1,083
Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology
Buonocore, S. M., Ahern, P. P., Uhlig, H. H., Ivanov, I. I., Littman, D. R., Maloy, K. J., & Powrie, F. M. (2010) · Nature · doi:10.1038/nature08949 · Cited by 1,066
Sanos, S. L., Bui, V. L., Mortha, A., Oberle, K., Heners, C., Johner, C., & Diefenbach, A. (2008) · Nature Immunology · doi:10.1038/ni.1684 · Cited by 873
Spits, H., & Santo, J. P. D. (2010) · Nature Immunology · doi:10.1038/ni.1962 · Cited by 840
Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation
Li, Y., Innocentin, S., Withers, D. R., Roberts, N. A., Gallagher, A., Grigorieva, E. F., Wilhelm, C., & Veldhoen, M. (2011) · Cell · doi:10.1016/j.cell.2011.09.025 · Cited by 837
Lymphoid tissue inducer–like cells are an innate source of IL-17 and IL-22
Takatori, H., Kanno, Y., Watford, W. T., Tato, C. M., Weiss, G. E., Ivanov, I. I., Littman, D. R., & O’Shea, J. J. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072713 · Cited by 769
Apetoh, L., Quintana, F. J., Pot, C., Joller, N., Xiao, S., Kumar, D., Burns, E. J., Sherr, D. H., Weiner, H. L., & Kuchroo, V. K. (2010) · Nature Immunology · doi:10.1038/ni.1912 · Cited by 725
The Search for Endogenous Activators of the Aryl Hydrocarbon Receptor
Nguyen, L. P., & Bradfield, C. A. (2007) · Chemical Research in Toxicology · doi:10.1021/tx7001965 · Cited by 718
Self-citationNguyen, N. T., Kimura, A., Nakahama, T., Chinen, I., Masuda, K., Nohara, K., Fujii‐Kuriyama, Y., & Kishimoto, T. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014465107 · Cited by 705
Vonarbourg, C., Mortha, A., Bui, V. L., Hernández, P. P., Kiss, E. A., Hoyler, T., Flach, M., Bengsch, B., Thimme, R., Hölscher, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.017 · Cited by 669
New insights into the development of lymphoid tissues
van de Pavert, S. A., & Mebius, R. E. (2010) · Nature reviews. Immunology · doi:10.1038/nri2832 · Cited by 616
Sawa, S., Lochner, M., Satoh‐Takayama, N., Dulauroy, S., Berard, M., Kleinschek, M. A., Cua, D., Santo, J. P. D., & Eberl, G. (2011) · Nature Immunology · doi:10.1038/ni.2002 · Cited by 596
Kimura, A., Naka, T., Nohara, K., Fujii‐Kuriyama, Y., & Kishimoto, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804231105 · Cited by 561
Luci, C., Reynders, A., Ivanov, I. I., Cognet, C., Chiche, L., Chasson, L., Hardwigsen, J., Anguiano, E., Banchereau, J., Chaussabel, D., et al. (2008) · Nature Immunology · doi:10.1038/ni.1681 · Cited by 551
Veldhoen, M., Hirota, K., Christensen, J. R., O’Garra, A., & Stockinger, B. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081438 · Cited by 548
Lineage Relationship Analysis of RORγt + Innate Lymphoid Cells
Sawa, S., Cherrier, M., Lochner, M., Satoh‐Takayama, N., Fehling, H. J., Vives, F. L., Santo, J. P. D., & Eberl, G. (2010) · Science · doi:10.1126/science.1194597 · Cited by 502
Hamada, H., Hiroi, T., Nishiyama, Y., Takahashi, H., Masunaga, Y., Hachimura, S., Kaminogawa, S., Takahashi‐Iwanaga, H., Iwanaga, T., Kiyono, H., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.1.57 · Cited by 481
The aryl hydrocarbon receptor in immunity
Esser, C., Rannug, A., & Stockinger, B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.06.005 · Cited by 447
Quintana, F. J., Murugaiyan, G., Farez, M., Mitsdoerffer, M., Tukpah, A.-M. C., Burns, E. J., & Weiner, H. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009201107 · Cited by 437
The aryl hydrocarbon receptor: a perspective on potential roles in the immune system
Stevens, E. A., Mezrich, J. D., & Bradfield, C. A. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03054.x · Cited by 425
Self-citationSatoh‐Takayama, N., Lesjean‐Pottier, S., Vieira, P., Sawa, S., Eberl, G., Vosshenrich, C. A. J., & Santo, J. P. D. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20092029 · Cited by 307
Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells
Possot, C., Schmutz, S., Chea, S., Boucontet, L., Louise, A., Cumano, A., & Golub, R. (2011) · Nature Immunology · doi:10.1038/ni.2105 · Cited by 246
Hughes, T. L., Becknell, B., Freud, A. G., McClory, S., Briercheck, E. L., Yu, J., Mao, C., Giovenzana, C., Nuovo, G. J., Wei, L., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.06.007 · Cited by 222
Boverhof, D. R., Burgoon, L. D., Tashiro, C. H. M., Sharratt, B., Chittim, B. G., Harkema, J. R., Mendrick, D. L., & Zacharewski, T. R. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfl100 · Cited by 203
The role of the nuclear hormone receptor RORγt in the development of lymph nodes and Peyer's patches
Eberl, G., & Littman, D. R. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00074.x · Cited by 192
External influences on the immune system via activation of the aryl hydrocarbon receptor
Stockinger, B., Hirota, K., Duarte, J. H., & Veldhoen, M. (2011) · Seminars in Immunology · doi:10.1016/j.smim.2011.01.008 · Cited by 190
Regulation of T Cell Activation by Notch Ligand, DLL4, Promotes IL-17 Production and Rorc Activation
Mukherjee, S., Schaller, M. A., Neupane, R., Kunkel, S. L., & Lukacs, N. W. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804322 · Cited by 188
AHR-mediated immunomodulation: The role of altered gene transcription
Kerkvliet, N. I. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.11.021 · Cited by 181
Notch signaling drives IL-22 secretion in CD4 + T cells by stimulating the aryl hydrocarbon receptor
Alam, M. S., Maekawa, Y., Kitamura, A., Tanigaki, K., Yoshimoto, T., Kishihara, K., & Yasutomo, K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911755107 · Cited by 166
Ota, N., Wong, K., Valdez, P. A., Zheng, Y., Crellin, N. K., Diehl, L. J., & Ouyang, W. (2011) · Nature Immunology · doi:10.1038/ni.2089 · Cited by 164
Notch Signaling Regulates Mouse and Human Th17 Differentiation
Keerthivasan, S., Suleiman, R., Lawlor, R. G., Roderick, J. E., Bates, T. C., Minter, L. M., Anguíta, J., Juncadella, I. J., Nickoloff, B. J., Poole, I. C. L., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003658 · Cited by 150
The development of intestinal lymphoid tissues at the interface of self and microbiota
Eberl, G., & Lochner, M. (2009) · Mucosal Immunology · doi:10.1038/mi.2009.114 · Cited by 149
Notch-Hes1 pathway is required for the development of IL-17–producing γδ T cells
Shibata, K., Yamada, H., Sato, T., Dejima, T., Nakamura, M., Ikawa, T., Hara, H., Yamasaki, S., Kageyama, R., Iwakura, Y., et al. (2011) · Blood · doi:10.1182/blood-2011-02-334995 · Cited by 143
Asquith, M. J., & Powrie, F. M. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20101330 · Cited by 141
Dere, E., Lo, R., Celius, T., Matthews, J. B., & Zacharewski, T. R. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-365 · Cited by 128
IL‐22 and inflammation: Leukin' through a glass onion
Zenewicz, L. A., & Flavell, R. A. (2008) · European Journal of Immunology · doi:10.1002/eji.200838655 · Cited by 104
CCR6 identifies lymphoid tissue inducer cells within cryptopatches
Lügering, A., Ross, M., Sieker, M., Heidemann, J., Williams, I. R., Domschke, W., & Kucharzik, T. F. (2010) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2010.04103.x · Cited by 55
Microbial control of regulatory and effector T cell responses in the gut
Hand, T. W., & Belkaid, Y. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.01.008 · Cited by 31
Wang, C., McDonough, J. S., McDonald, K. G., Huang, C. C., & Newberry, R. D. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.6.4052 · Cited by 28
Self-citationInduction of intestinal lymphoid tissue formation by intrinsic and extrinsic signals
Finke, D. (2009) · Seminars in Immunopathology · doi:10.1007/s00281-009-0163-6 · Cited by 23
Flagged first, then by citations
Cited by
Sorted by citations
Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.003 · Cited by 2,614
Innate Lymphoid Cells: 10 Years On
Vivier, É., Artis, D., Colonna, M., Diefenbach, A., Santo, J. P. D., Eberl, G., Koyasu, S., Locksley, R. M., McKenzie, A. N. J., Mebius, R. E., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.017 · Cited by 2,136
Self-citationRegional specialization within the intestinal immune system
Mowat, A. M., & Agace, W. W. (2014) · Nature reviews. Immunology · doi:10.1038/nri3738 · Cited by 1,882
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease
Pickard, J. M., Zeng, M. Y., Caruso, R., & Núñez, G. (2017) · Immunological Reviews · doi:10.1111/imr.12567 · Cited by 1,699
The biology of innate lymphoid cells
Artis, D., & Spits, H. (2015) · Nature · doi:10.1038/nature14189 · Cited by 1,691
Metadata
- 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
- ORCID
- Venue
- Nature Immunology
- Published
- 2011-11-20
- Volume
- 13
- Issue
- 2
- Pages
- 144-151
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3468413
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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
- Health Sciences › Medicine › Gastroenterology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review