The Aryl Hydrocarbon Receptor Regulates Gut Immunity through Modulation of Innate Lymphoid Cells

By J. Qiu, Jennifer J. Heller, Xiaohuan Guo, Zong-ming E. Chen, Kamonwan Fish, yang-xin fu, Liang Zhou. Immunity, 2011

829 citations recorded by the source corpus.

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.

Subfields: Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/1935a00e78fa0b4ae809e5f5dfc8634972a8578d

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Citations in the corpus

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).”
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).”
Homeostatic immunity and the microbiota (2017, neutral): “Within the gastrointestinal tract, AhR-activation promotes IL-22 production by group 3 innate lymphoid cells (ILC) and Th17 cells (Kiss et al., 2011; Qiu et al., 2012; Veldhoen et al., 2008; Zelante et al., 2013), and the maintenance of intra-epithelial Belkaid and Harrison Page 4”
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. (2018, positive): “Similarly, the degradation of AhR ligands in response to Cyp1A1 dysregulation as well as the deletion of AhR lead to increased susceptibility to Citrobacter rodentium infection (Qiu et al., 2012; Schiering et al., 2017).”
Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism (2018, background): “Similarly, in the absence of AhR, mice show high disease susceptibility when infected by Listeria monocytogenes and Citrobacter rodentium (Shi et al., 2007; Qiu et al., 2012).”
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.”
Regulation of the immune response by the aryl hydrocarbon receptor (2018, background): “Conversely, AhR deficiency impairs IL-22 production by Th17 cells, probably reflecting the role of AhR in facilitating the recruitment of the transcription factor RORgt to the IL-22 promoter (Figure 3; Qiu et al., 2012; Veldhoen et al., 2008; Yeste et al., 2014).”
Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. (2013, positive): “In the gastrointestinal tract, dietderived AhR ligands promote local IL-22 production (Lee et al., 2012) by innate lymphoid cells (ILCs) (Qiu et al., 2012), now 372 Immunity 39, 372–385, August 22, 2013 ª2013 Elsevier Inc. referred to as group 3 ILCs (ILC3s) (Spits et al., 2013).”