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Aryl hydrocarbon receptor promotes RORγt+ Group 3 ILCs and controls intestinal immunity and inflammation

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Abstract

Unlike adaptive immune cells that require antigen recognition and functional maturation during infection, innate lymphoid cells (ILCs) usually respond to pathogens promptly and serve as the first line of defense in infectious diseases. RAR-related orphan receptor (RORγt)+ group 3 ILCs are one of the innate cell populations that have recently been intensively studied. During the fetal stage of development, RORγt+ group 3 ILCs (e.g., lymphoid tissue inducer cells) are required for lymphoid organogenesis. In adult mice, RORγt+ group 3 ILCs are abundantly present in the gut to exert immune defensive functions. Under certain circumstances, however, RORγt+ group 3 ILCs can be pathogenic and contribute to intestinal inflammation. Aryl hydrocarbon receptor (Ahr), a ligand-dependent transcriptional factor, is widely expressed by various immune and non-immune cells. In the gut, the ligand for Ahr can be derived/generated from diet, microflora, and/or host cells. Ahr has been shown to regulate different cell populations in the immune system including RORγt+ group 3 ILCs, T helper (Th)17/22 cells, γδT cells, regulatory T cells (Tregs), Tr1 cells, and antigen presenting cells. In this review, we will focus on the development and function of RORγt+ group 3 ILCs, and discuss the role of Ahr in intestinal immunity and inflammation in mice and in humans. A better understanding of the function of Ahr in the gut is important for developing new therapeutic means to target Ahr in future treatment of infectious and autoimmune diseases.

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Acknowledgments

We thank all members of the Zhou Laboratory for their helpful discussion. This work was supported by the National Institutes of Health (AI089954 and AI091962 to LZ) and by a Cancer Research Institute Investigator Award (LZ). Liang Zhou is a Pew Scholar in Biomedical Sciences, supported by the Pew Charitable Trusts.

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  1. Department of Pathology, Feinberg School of Medicine, Northwestern University, 300 E. Superior Street, Chicago, IL, 60611, USA

    Ju Qiu & Liang Zhou

  2. Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 300 E. Superior Street, Chicago, IL, 60611, USA

    Ju Qiu & Liang Zhou

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  1. Ju Qiu
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Correspondence to Liang Zhou.

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This article is a contribution to the special issue on Roles of Aryl Hydrocarbon Receptor in Controlling Immunity – Guest Editors: C. Pot, V. Kuchroo and F. Quintaña

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Qiu, J., Zhou, L. Aryl hydrocarbon receptor promotes RORγt+ Group 3 ILCs and controls intestinal immunity and inflammation. Semin Immunopathol 35, 657–670 (2013). https://doi.org/10.1007/s00281-013-0393-5

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