Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid
Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid
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DOI：
10.1126/science.1145697
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发表时间：
2007-07-13
期刊：
影响因子：
56.9
通讯作者：
Cheroutre, Hilde
中科院分区：
文献类型：
--
作者：
Mucida, Daniel;Park, Yunji;Cheroutre, Hilde
细胞因子转化生长因子-β（TGF-β）将初始T细胞转化为防止自身免疫的调节性T（Treg）细胞。然而，在白细胞介素-6（IL-6）的存在下，还发现TGF-β促进幼稚T淋巴细胞分化为促炎性IL-17生成烟碱的T辅助17（TH 17）细胞，其促进自身免疫和炎症。这就提出了一个问题，即TGF-β如何产生如此独特的结果。我们鉴定了维生素A代谢物视黄酸作为TGF-β依赖性免疫应答的关键调节剂，能够抑制IL-6驱动的促炎性TH 17细胞的诱导并促进抗炎性Treg细胞分化。这些发现表明，一种共同的代谢物可以调节促炎免疫和抗炎免疫之间的平衡。
The cytokine transforming growth factor-beta (TGF-beta) converts naive T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-beta has also been found to promote the differentiation of naive T lymphocytes into proinflammatory IL-17 cytokine-producing T helper 17 (TH17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-beta can generate such distinct outcomes. We identified the vitamin A metabolite retinoic acid as a key regulator of TGF-beta-dependent immune responses, capable of inhibiting the IL-6-driven induction of proinflammatory TH17 cells and promoting anti-inflammatory Treg cell differentiation. These findings indicate that a common metabolite can regulate the balance between pro- and anti-inflammatory immunity.