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

R Gandhi, D Kumar, EJ Burns, M Nadeau, B Dake… - Nature …, 2010 - nature.com
R Gandhi, D Kumar, EJ Burns, M Nadeau, B Dake, A Laroni, D Kozoriz, HL Weiner…
Nature immunology, 2010nature.com
The aryl hydrocarbon receptor (AhR) participates in the differentiation of mouse regulatory T
cells (Treg cells) and interleukin 17 (IL-17)-producing helper T cells (TH17 cells), but its role
in human T cell differentiation is unknown. We investigated the role of AhR in the
differentiation of human induced Treg cells (iTreg 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 …
Abstract
The aryl hydrocarbon receptor (AhR) participates in the differentiation of mouse regulatory T cells (Treg cells) and interleukin 17 (IL-17)-producing helper T cells (TH17 cells), but its role in human T cell differentiation is unknown. We investigated the role of AhR in the differentiation of human induced Treg cells (iTreg 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-β1 induced Foxp3+ iTreg cells, which suppress responder T cells through the ectonucleoside triphosphate diphosphohydrolase CD39. The induction of functional Foxp3+ iTreg cells required coordinated action of the transcriptional regulators Smad1 and Aiolos. Thus, AhR is a potential target through which functional iTreg cells could be induced in human autoimmune disorders.
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