Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor

Regulatory T cells (T-reg) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of T-reg cells is reciprocally related to that of pro- inflammatory T cells producing interleukin- 17 ( T(H)17). Although T-reg cell dysfunction and/ or T(H)17 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 T-reg and T(H)17 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 T-reg cell development, boosted T(H)17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both T-reg and T(H)17 cell differentiation in a ligand- specific fashion, constituting a unique target for therapeutic immunomodulation.