title: Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase.
abstract: Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to immune suppression associated with the induction of regulatory T cells (T(reg)) expressing the transcription factor Foxp3. The immunological mechanisms of suppression are not well understood however dendritic cells (DC) are considered a key target for AhR-mediated immune suppression. Here we show that activation of AhR by TCDD induces DC indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase-like protein (IDO2). Induction of IDO1 and IDO2 was also found in lung and spleen associated with an increase of the T(reg) marker Foxp3 in spleen of TCDD-treated C57BL/6 mice, which is suppressed by inhibition of IDO. These data indicate that AhR-activation is an important signaling pathway for IDO expression and suggest a critical role of IDO in the mechanism leading to the generation of T(reg) that mediates the immune suppression through activation of AhR.
authors.affiliation: Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Christoph F A
authors.initials: CF
authors.lastname: Vogel
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Goth
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D007371:Interferon-gamma