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Title[redir]:
Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor | Nature
Description:
Regulatory T cells (Treg) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of Treg cells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (TH17). Although Treg cell dysfunction and/or TH17 cell dysregulation are thought to contribute to the development of autoimmune disorders, little is known about the physiological pathways that control the generation of these cell lineages. Here we report the identification of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) as a regulator of Treg and TH17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional Treg cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with Treg cell development, boosted TH17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both Treg and TH17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation. The aryl hydrocarbon receptor (AHR) is a transcription factor best known for mediating the toxicity of aromatic hydrocarbons such as dioxin: its activation leads to the production of detoxification enzymes. AHR has been intensely studied in relation to toxicology and cancer research, but no mechanistic connection to the immune system was known. Now two groups report a role for AHR in maintaining the balance between two T-lymphocyte populations — the Treg and TH17 cells — that are part of the immune regulation system dealing with tolerance of self-antigens and pathogen clearance. Both groups also show that AHR affects the severity of experimental autoimmune encephalitis, a mouse model of multiple sclerosis. This work raises the possibility that stimulation of AHR by environmental factors could be involved in the development of autoimmune disease, and point to AHR as a possible drug target for immunomodulation. The aryl hydrocarbon receptor (AHR) is the cellular receptor for a number of environment contaminants. It is shown here to induce regulatory T cells when bound to the ligand TCCD and promote TH17 differentiation when bound to FICZ.
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Keywords {🔍}
article, google, scholar, cas, nature, cells, cell, receptor, regulatory, aryl, hydrocarbon, ahr, ads, treg, differentiation, foxp, development, autoimmune, content, activation, access, control, regulation, immunol, usa, cookies, analysis, transcription, factor, immune, pharmacol, privacy, information, mice, human, expression, proc, natl, acad, sci, immunity, mol, function, data, quintana, korn, bettelli, system, pathways, experimental,
Topics {✒️}
nature portfolio permissions reprints cancer research privacy policy advertising social media author information authors transforming growth factor-β1 8-tetrachlorodibenzo-p-dioxin generates forkhead/winged-helix protein nature genet nature med author correspondence nature immunol fork head-related protein foxp3 transcription-factor-dependent multiple-sequence local alignment peripheral cd4+cd25- naive nature 448 nature 441 nature 423 nature 453 nature personal data data protection springerlink instant access permissions myelin-specific regulatory activated dioxin receptor experimental autoimmune encephalomyelitis single-cell analysis aryl hydrocarbon receptor cell transcriptional signature t-lymphocyte populations transcription factor foxp3 experimental autoimmune encephalitis retinoic acid privacy treg cell development human cyp1a2 gene tgf-β induction control autoimmune inflammation creb/atf-dependent ligand-dependent interactions oestrogen receptor signalling cell differentiation mediated reciprocal developmental pathways cytosolic ah receptor cell cycle progression divergent signaling pathways
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