Microenvironment and Immunity Unit, Institut Pasteur, 75724, Paris, France.
INSERM U1224, 75724, Paris, France.
J Microbiol. 2018 Mar;56(3):163-171. doi: 10.1007/s12275-018-7565-x. Epub 2018 Feb 28.
The mammalian gastrointestinal tract accommodates trillions of bacteria, many of which provide beneficial effects to the host, including protection from pathogenic microorganisms and essential metabolites. However, the intestinal immune system needs to adapt to the constantly fluctuating microbial environment at mucosal surfaces in order to maintain homeostasis. In particular, the gut microbiota induces the differentiation of effector Th17 cells and regulatory T cells (Tregs) that express RORγt, the master regulator of antimicrobial type 3 immunity. RORγt Tregs constitute a major population of colonic Tregs that is distinct from thymusderived Tregs and require bacterial antigens for differentiation. The balance between Th17 cells and RORγt Tregs, that is, the tone of the local type 3 immune response, is regulated by the vitamin A metabolite retinoic acid produced by the host. Furthermore, Th17 cells and RORγt Tregs regulate intestinal type 2 immune responses, explaining how bacteria block allergic reactions. Here, we review the cellular and molecular mechanisms involved in the differentiation, regulation and function of RORγt (type 3) Tregs, and discuss the multiple equilibria that exist between effector T cells and Tregs, as well as between different types of immune responses, which are necessary to maintain homeostasis and health.
哺乳动物的胃肠道容纳了数以万亿计的细菌，其中许多对宿主有益，包括防止病原微生物和必需代谢物的侵害。然而，肠道免疫系统需要适应黏膜表面不断变化的微生物环境，以维持体内平衡。特别是，肠道微生物群诱导效应性 Th17 细胞和表达 RORγt 的调节性 T 细胞（Tregs）的分化，RORγt 是抗微生物型 3 免疫的主要调节因子。RORγt Tregs 构成了结肠 Tregs 的主要群体，与胸腺衍生的 Tregs 不同，并且需要细菌抗原分化。Th17 细胞和 RORγt Tregs 之间的平衡，即局部型 3 免疫反应的基调，受宿主产生的维生素 A 代谢产物视黄酸调节。此外，Th17 细胞和 RORγt Tregs 调节肠道型 2 免疫反应，解释了细菌如何阻断过敏反应。在这里，我们回顾了 RORγt（型 3）Tregs 的分化、调节和功能涉及的细胞和分子机制，并讨论了效应 T 细胞和 Tregs 之间以及不同类型免疫反应之间存在的多个平衡，这是维持体内平衡和健康所必需的。
