Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells

Nat Immunol. 2010 Sep;11(9):846-53. doi: 10.1038/ni.1915. Epub 2010 Aug 1.


The aryl hydrocarbon receptor (AhR) participates in the differentiation of mouse regulatory T cells (T(reg) cells) and interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells), but its role in human T cell differentiation is unknown. We investigated the role of AhR in the differentiation of human induced T(reg) cells (iT(reg) cells). We found that AhR activation promoted the differentiation of CD4(+)Foxp3(-) T cells, which produce IL-10 and control responder T cells through granzyme B. However, activation of AhR in the presence of transforming growth factor-beta1 induced Foxp3(+) iT(reg) cells, which suppress responder T cells through the ectonucleoside triphosphate diphosphohydrolase CD39. The induction of functional Foxp3(+) iT(reg) cells required coordinated action of the transcriptional regulators Smad1 and Aiolos. Thus, AhR is a potential target through which functional iT(reg) cells could be induced in human autoimmune disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Lymphocyte Activation / immunology*
  • Promoter Regions, Genetic
  • Receptors, Aryl Hydrocarbon / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, Aryl Hydrocarbon
  • Interleukin-10