Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor - PubMed (original) (raw)

. 2008 May 1;453(7191):65-71.

doi: 10.1038/nature06880. Epub 2008 Mar 23.

Affiliations

• PMID: 18362915
• DOI: 10.1038/nature06880

Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor

Francisco J Quintana et al. Nature. 2008.

Abstract

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 T(reg) 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.

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Comment in

• Immunology: T cells hang in the balance.
  Stevens EA, Bradfield CA. Stevens EA, et al. Nature. 2008 May 1;453(7191):46-7. doi: 10.1038/453046a. Nature. 2008. PMID: 18451850 No abstract available.
• Literature watch: implications for transplantation. AHR and tryptophan catabolism: putting the effector T-cell response to sleep.
  Alessandrini A, Bromberg JS. Alessandrini A, et al. Am J Transplant. 2012 Apr;12(4):801. doi: 10.1111/j.1600-6143.2012.04058.x. Am J Transplant. 2012. PMID: 22458381 No abstract available.

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