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

FJ Quintana, AS Basso, AH Iglesias, T Korn, MF Farez… - Nature, 2008 - nature.com
FJ Quintana, AS Basso, AH Iglesias, T Korn, MF Farez, E Bettelli, M Caccamo, M Oukka…
Nature, 2008nature.com
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 …
Abstract
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.
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