title: The roles of aryl hydrocarbon receptor in immune responses.
abstract: A number of recent studies have examined the functions of aryl hydrocarbon receptor (Ahr) in the immune system. Also known as dioxin receptor, Ahr is a ligand-activated transcription factor that serves as a receptor for various environmental toxins. The functions of Ahr in T cells depend on the specific ligand bound to the receptor. For instance, binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to Ahr suppresses experimental autoimmune encephalomyelitis (EAE) by promoting the development of Foxp3(+) Treg cells, whereas 6-formylindolo[3,2-b]carbazole enhances EAE by inducing the differentiation of IL-17-producing T cells. Furthermore, specifically deleting Ahr in T cells inhibits collagen-induced arthritis in mice. In macrophages and dendritic cells (DCs), Ahr is anti-inflammatory. In response to LPS, Ahr-deficient macrophages show increased production of pro-inflammatory cytokines, such as IL-6 and TNF-α, and Ahr-deficient DCs produce less of the anti-inflammatory cytokine IL-10. In this review, we discuss the roles of Ahr in macrophages and T cells. Moreover, studies examining Ahr activation in other cell types have revealed additional contributions to B cell and osteoblast/osteoclast differentiation. We also briefly summarize the current understanding of regulatory mechanisms underlying Ahr activation in various cells and discuss the potential clinical implications of cell-specific targeting of Ahr in pathologic conditions of the immune system.
authors.affiliation: Laboratory of Immune Regulation, WPI-Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Nam Trung
authors.initials: NT
authors.lastname: Nguyen
authors.forename: Hamza
authors.initials: H
authors.lastname: Hanieh
authors.forename: Taisuke
authors.initials: T
authors.lastname: Nakahama
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018336:Receptors, Aryl Hydrocarbon
keywords: dioxin receptor; immune regulation