Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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.
芳香烃受体 (AhR) 参与调节性 T 细胞 (Treg 细胞) 和白细胞介素 17 (IL-17) 产生的辅助性 T 细胞 (T(H)17 细胞) 的分化,但它在人类 T 细胞分化中的作用尚不清楚。我们研究了 AhR 在人诱导性 T 调节细胞 (iTreg 细胞) 分化中的作用。我们发现 AhR 的激活促进了 CD4+Foxp3- T 细胞的分化,这些细胞通过颗粒酶 B 产生 IL-10 并控制应答性 T 细胞。然而,在转化生长因子-β1 存在的情况下激活 AhR 诱导 Foxp3+iTreg 细胞,通过外核苷酸三磷酸二磷酸水解酶 CD39 抑制应答性 T 细胞。功能性 Foxp3+iTreg 细胞的诱导需要转录调节因子 Smad1 和 Aiolos 的协调作用。因此,AhR 是一个潜在的靶点,可以通过它在人类自身免疫性疾病中诱导功能性 iTreg 细胞。