Department of Immunology, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Internal Medicine Research Unit, Worldwide Research, Development & Medical, Pfizer Inc., Cambridge, MA, USA.
Immunity. 2023 Apr 11;56(4):829-846.e8. doi: 10.1016/j.immuni.2023.01.033. Epub 2023 Feb 22.
Specific microbial signals induce the differentiation of a distinct pool of RORγ regulatory T (Treg) cells crucial for intestinal homeostasis. We discovered highly analogous populations of microbiota-dependent Treg cells that promoted tissue regeneration at extra-gut sites, notably acutely injured skeletal muscle and fatty liver. Inflammatory meditators elicited by tissue damage combined with MHC-class-II-dependent T cell activation to drive the accumulation of gut-derived RORγ Treg cells in injured muscle, wherein they regulated the dynamics and tenor of early inflammation and helped balance the proliferation vs. differentiation of local stem cells. Reining in IL-17A-producing T cells was a major mechanism underlying the rheostatic functions of RORγ Treg cells in compromised tissues. Our findings highlight the importance of gut-trained Treg cell emissaries in controlling the response to sterile injury of non-mucosal tissues.
特定的微生物信号诱导 RORγ 调节性 T（Treg）细胞的分化，这对于肠道内稳态至关重要。我们发现了高度类似的依赖于微生物群的 Treg 细胞群，它们在肠道外部位促进组织再生，特别是急性损伤的骨骼肌和脂肪肝。组织损伤引起的炎症介质与 MHC 类 II 依赖性 T 细胞激活相结合，驱动肠道来源的 RORγ Treg 细胞在损伤肌肉中的积累，在那里它们调节早期炎症的动态和特征，并有助于平衡局部干细胞的增殖与分化。抑制产生 IL-17A 的 T 细胞是 RORγ Treg 细胞在受损组织中发挥变阻器功能的主要机制。我们的研究结果强调了肠道训练的 Treg 细胞在控制非黏膜组织无菌损伤反应中的重要性。
