Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells.
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.
Gandhi
Roopali
R
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Kumar
Deepak
D
Burns
Evan J
EJ
Nadeau
Meghan
M
Dake
Ben
B
Laroni
Alice
A
Kozoriz
Deneen
D
Weiner
Howard L
HL
Quintana
Francisco J
FJ
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018336:Receptors, Aryl Hydrocarbon; D016753:Interleukin-10