TY - JOUR
T1 - Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor
AU - Quintana, Francisco J.
AU - Basso, Alexandre S.
AU - Iglesias, Antonio H.
AU - Korn, Thomas
AU - Farez, Mauricio F.
AU - Bettelli, Estelle
AU - Caccamo, Mario
AU - Oukka, Mohamed
AU - Weiner, Howard L.
N1 - Funding Information:
Acknowledgements We thank L. I. Zon for helpful discussions and for the critical review of this manuscript; D. Kozoriz and J. P. Schatzmann Peron for help with FACS analysis; and D. Sherr and I. R. Cohen for useful discussions. This work was supported by grants AI435801 and NS38037 from the National Institutes of Health to H.L.W., TA3014A1/1 from the National Multiple Sclerosis Society to E.B. and R01AI073542-01 from the National Institutes of Health and RG-3882-A-1 from the National Multiple Sclerosis Society to M.O. F.J.Q. is a recipient of a long-term fellowship from the Human Frontiers of Science Program Organization; T.K. was supported by the Deutsche Forschungsgemeinschaft (KO 2964/1-1).
PY - 2008/5/1
Y1 - 2008/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=42649095378&partnerID=8YFLogxK
U2 - 10.1038/nature06880
DO - 10.1038/nature06880
M3 - Article
C2 - 18362915
AN - SCOPUS:42649095378
SN - 0028-0836
VL - 453
SP - 65
EP - 71
JO - Nature
JF - Nature
IS - 7191
ER -