Department of Cellular Immunology, Clinic for Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
German Rheumatism Research Center (DRFZ) Berlin, Leibniz Association, Berlin, Germany.
Nat Immunol. 2019 Apr;20(4):471-481. doi: 10.1038/s41590-019-0316-2. Epub 2019 Feb 18.
Foxp3 regulatory T cells (T cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal T cells to constrain microbiota-dependent interleukin (IL)-17-producing helper T cell (T17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal T cell populations, including RORγt T cells and follicular regulatory T cells, were c-Maf dependent. c-Maf controlled T cell-derived IL-10 production and prevented excessive signaling via the kinases PI(3)K (phosphatidylinositol-3-OH kinase) and Akt and the metabolic checkpoint kinase complex mTORC1 (mammalian target of rapamycin) and expression of inflammatory cytokines in intestinal T cells. c-Maf deficiency in T cells led to profound dysbiosis of the intestinal microbiota, which when transferred to germ-free mice was sufficient to induce exacerbated intestinal T17 responses, even in a c-Maf-competent environment. Thus, c-Maf acts to preserve the identity and function of intestinal T cells, which is essential for the establishment of host-microbe symbiosis.
叉头框蛋白 P3 调节性 T 细胞（T 细胞）对于维持淋巴组织和非淋巴组织中的免疫稳态至关重要。在这里，我们证明了肠道 T 细胞限制依赖于微生物群的白细胞介素（IL）-17 产生辅助性 T 细胞（T17 细胞）和免疫球蛋白 A 反应的能力，关键需要转录因子 c-Maf 的表达。几种肠道 T 细胞群的终末分化和功能，包括 RORγt T 细胞和滤泡调节性 T 细胞，都依赖于 c-Maf。c-Maf 控制 T 细胞衍生的 IL-10 产生，并防止通过激酶 PI(3)K（磷脂酰肌醇-3-OH 激酶）和 Akt 以及代谢检查点激酶复合物 mTORC1（雷帕霉素的哺乳动物靶标）和肠道 T 细胞中炎症细胞因子的过度信号传导。T 细胞中 c-Maf 的缺失导致肠道微生物群的严重失调，当将其转移到无菌小鼠中时，足以诱导过度的肠道 T17 反应，即使在 c-Maf 有功能的环境中也是如此。因此，c-Maf 作用是维持肠道 T 细胞的特性和功能，这对于建立宿主-微生物共生关系至关重要。
