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The Aryl Hydrocarbon Receptor Regulates Gut Immunity through Modulation of Innate Lymphoid Cells
Open accessAbstract
SUMMARY Innate lymphoid cells (ILCs) expressing the nuclear receptor RORγt are essential for gut immunity presumably through production of interleukin (IL)-22. The molecular mechanism underlying the development of RORγt+ ILCs is poorly understood. Here, we have shown that the aryl hydrocarbon receptor (Ahr) plays an essential role in RORγt+ ILC maintenance and function. Expression of Ahr in the hematopoietic compartment was important for accumulation of adult but not fetal intestinal RORγt+ ILCs. Without Ahr, RORγt+ ILCs had increased apoptosis and less production of IL-22. RORγt interacted with Ahr and promoted Ahr binding at the Il22 locus. Upon IL-23 stimulation, Ahr-deficient RORγt+ ILCs had reduced IL-22 expression, consistent with downregulation of IL-23R in those cells. Ahr-deficient mice succumbed to Citrobacter rodentium infection, while ectopic expression of IL-22 protected animals from early mortality. Our data uncover a previously unrecognized physiological role for Ahr in promoting innate gut immunity by regulating RORγt+ ILCs.
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Cites
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Self-citationKorn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087
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
Phenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861
Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells
Acosta-Rodriguez, E. V., Rivino, L., Geginat, J., Jarrossay, D., Gattorno, M., Lanzavecchia, A., Sallusto, F., & Napolitani, G. (2007) · Nature Immunology · doi:10.1038/ni1467 · Cited by 1,828
The 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
Definition of a Dioxin Receptor Mutant That Is a Constitutive Activator of Transcription
McGuire, J., Okamoto, K., Whitelaw, M. L., Tanaka, H., & Poellinger, L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105607200 · Cited by 102 · cited 2×
“CA-Ahr lacks the PAS-B domain, enabling it to constitutively dimerize with Arnt, bind to DNA, and activate transcription in a ligandindependent manner (McGuire et al., 2001).”
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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
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Maynard, C. L., Elson, C. O., Hatton, R. D., & Weaver, C. T. (2012) · Nature · doi:10.1038/nature11551 · Cited by 1,598
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Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876
“…Candida albicans; exacerbated DSS-induced colitis; and even altered susceptibility to experimental autoimmune encephalomyelitis (EAE) (Kiss et al., 2011; Lee et al., 2011; Li et al., 2011; Qiu et al., 2012; Rothhammer et al., 2016; Shi et al., 2007; Veldhoen et al., 2008; Zelante et al., 2013).”
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Eberl, G., Colonna, M., Di Santo, J. P., & McKenzie, A. N. J. (2015) · Science · doi:10.1126/science.aaa6566 · Cited by 878
Natividad, J. M., Agus, A., Planchais, J., Lamas, B., Jarry, A. C., Martin, R., Michel, M.-L., Chong-Nguyen, C., Roussel, R., Straube, M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.001 · Cited by 642
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Metidji, A., Omenetti, S., Crotta, S., Li, Y., Nye, E., Ross, E., Li, V., Maradana, M. R., Schiering, C., & Stockinger, B. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.010 · Cited by 402
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BackgroundColonization and effector functions of innate lymphoid cells in mucosal tissues
Kim, M., & Kim, C. H. (2016) · Microbes and Infection · doi:10.1016/j.micinf.2016.06.005 · Cited by 16
Metadata
- Authors
- Qiu, J., Heller, J. J., Guo, X., Chen, Z.-M. E., Fish, K., Fu, Y.-X., & Zhou, L.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 36
- Issue
- 1
- Pages
- 92-104
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1981177186
- Cited by
- 859
- References
- 8
- FWCI
- 16.44
- Type
- journal article
- Language
- en
- Open access
- bronze
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