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Aryl hydrocarbon receptor and experimental autoimmune arthritis

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Abstract

Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses. Many Ahr-mediated immune regulatory mechanisms have been discovered, which will likely enhance our understanding of the molecular pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). RA is a systemic inflammatory disease that affects approximately 1 % of the population and is characterized by chronic inflammation of the synovium and subsequent joint destruction. Recent findings showed that Ahr plays critical roles in the development of Th17 cells, which are key effector T cells in a variety of human autoimmune diseases including RA. Consistent with these findings, our previous study demonstrated that Ahr in T cells is important for the development of collagen-induced arthritis, a widely used murine model of human RA, possibly via the induction of Th17 cells. In addition, Ahr is an attractive molecule because tobacco smoke is a well-known environmental risk factor for RA development and Ahr agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methyl cholanthrene, and benzo[a]pyrene, are major toxic components in cigarettes. This review summarizes recent findings on Ahr functions in immune cells in the context of RA pathogenesis during stimulation with smoking-derived ligands. We also discuss the potential link between Ahr and novel factors, such as microRNAs, in the development of RA, thereby providing further mechanistic insight into this autoimmune disorder.

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Acknowledgments

This work was supported by the Program for Promotion of Fundamental Studies in Health Sciences from the National Institute of Biomedical Innovation, and a Grant-in-Aid for Scientific Research (KAKENHI) 24790471 (for N.T.N) from the Japan Society for the Promotion of Science (JSPS).

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  1. Laboratory of Immune Regulation, WPI-Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Nam Trung Nguyen, Taisuke Nakahama & Tadamitsu Kishimoto

  2. National Key Laboratory of Gene Technology, Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Cau Giay District, Ha Noi, Vietnam

    Nam Trung Nguyen

  3. Laboratory of RNA Function, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Taisuke Nakahama

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  1. Nam Trung Nguyen
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Correspondence to Tadamitsu Kishimoto.

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Nam Trung Nguyen and Taisuke Nakahama contributed equally to this paper.

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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Nguyen, N.T., Nakahama, T. & Kishimoto, T. Aryl hydrocarbon receptor and experimental autoimmune arthritis. Semin Immunopathol 35, 637–644 (2013). https://doi.org/10.1007/s00281-013-0392-6

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