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

Type 1 regulatory T cells control autoinflammatory diseases. In two linked papers, groups led by Kuchroo and Quintana demonstrate the role of the aryl hydrocarbon receptor in the differentiation of these 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-β1 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.