title: Aryl hydrocarbon receptor signaling regulates NF-κB RelB activation during dendritic-cell differentiation.
abstract: How the aryl hydrocarbon receptor (AhR) regulates dendritic-cell (DC) differentiation is unknown. We show that activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused enhanced differentiation from immature DCs (IDCs) to mature DCs (MDCs) in the bone-marrow-derived DCs (BMDC) from B6 wild-type mice but not in the BMDCs from AhR-null mice as indicated by the expression of CD11c and class II major histocompatibility complex (MHC). Enhanced maturation of BMDCs was associated with elevated levels of CD86 and an increased AhR-dependent nuclear accumulation of nuclear factor-kappa-light-chain enhancer of activated B cell (NF-κB) member RelB in BMDCs. The expression of interleukin (IL) 10 and chemokine DC-CK1 was suppressed, whereas that of CXCL2, CXCL3 and IL-22 was significantly increased in AhR-activated BMDCs. Furthermore, TCDD induced expression of the regulatory enzymes indoleamine 2,3-dioxygenase (IDO1) and indoleamine 2,3-dioxygenase-like 1 (IDO2). Increased expression of IDO2 was associated with coexpression of the cell-surface marker CCR6. Interestingly, mRNA expression of the chemokine receptor CCR6 was drastically decreased in AhR-null IDCs and MDCs. Overall, these data demonstrate that AhR modifies the maturation of BMDCs associated with the induction of the regulatory enzyme IDO and altered expression of cytokine, chemokines and DC-specific surface markers and receptors.
authors.affiliation: 1] Department of Environmental Toxicology, University of California at Davis, Davis, CA, USA [2] Center for Health and the Environment, University of California at Davis, Davis, CA, USA.
authors.forename: Christoph F A
authors.initials: CF
authors.lastname: Vogel
authors.forename: Dalei
authors.initials: D
authors.lastname: Wu
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Goth
authors.forename: Jaeeun
authors.initials: J
authors.lastname: Baek
authors.forename: Anna
authors.initials: A
authors.lastname: Lollies
authors.forename: Rowena
authors.initials: R
authors.lastname: Domhardt
authors.forename: Annemarie
authors.initials: A
authors.lastname: Grindel
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054399:Receptors, CCR6 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051841:Transcription Factor RelB / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D018925:Chemokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10; D007378:Interleukins; D016328:NF-kappa B; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D054399:Receptors, CCR6; D051841:Transcription Factor RelB; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C583637:IDO1 protein, mouse; C497594:Relb protein, mouse