17 cell differentiation by the aryl hydrocarbon receptor

来自 Springer

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223

作者：

FJ Quintana，AS Basso，AH Iglesias，T Korn，MF Farez，E Bettelli，M Caccamo，M Oukka，HL Weiner

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摘要：

Regulatory T cells (T) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of Tcells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (T17). Although Tcell dysfunction and/or T17 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 Tand T17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional Tcells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with Tcell development, boosted T17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both Tand T17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation.

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关键词：

Animals Mice, Inbred C57BL Humans Mice T-Lymphocytes, Helper-Inducer Encephalomyelitis, Autoimmune, Experimental Carbazoles Indoles Receptors, Aryl Hydrocarbon Ligands