MRC, Centre for Transplantation, King's College London, London, UK.
National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
Nat Immunol. 2018 Dec;19(12):1403-1414. doi: 10.1038/s41590-018-0230-z. Epub 2018 Nov 5.
Repair of tissue damaged during inflammatory processes is key to the return of local homeostasis and restoration of epithelial integrity. Here we describe CD161 regulatory T (T) cells as a distinct, highly suppressive population of T cells that mediate wound healing. These T cells were enriched in intestinal lamina propria, particularly in Crohn's disease. CD161 T cells had an all-trans retinoic acid (ATRA)-regulated gene signature, and CD161 expression on T cells was induced by ATRA, which directly regulated the CD161 gene. CD161 was co-stimulatory, and ligation with the T cell antigen receptor induced cytokines that accelerated the wound healing of intestinal epithelial cells. We identified a transcription-factor network, including BACH2, RORγt, FOSL2, AP-1 and RUNX1, that controlled expression of the wound-healing program, and found a CD161 T cell signature in Crohn's disease mucosa associated with reduced inflammation. These findings identify CD161 T cells as a population involved in controlling the balance between inflammation and epithelial barrier healing in the gut.
在炎症过程中受损组织的修复对于恢复局部内稳态和上皮完整性至关重要。在这里，我们描述了 CD161 调节性 T（T）细胞作为一种独特的、高度抑制性的 T 细胞群体，介导伤口愈合。这些 T 细胞在肠固有层中富集，特别是在克罗恩病中。CD161 T 细胞具有全反式视黄酸（ATRA）调节的基因特征，并且 ATRA 诱导 T 细胞上的 CD161 表达，其直接调节 CD161 基因。CD161 是共刺激分子，与 T 细胞抗原受体的结合诱导细胞因子，加速肠上皮细胞的伤口愈合。我们确定了一个转录因子网络，包括 BACH2、RORγt、FOSL2、AP-1 和 RUNX1，它控制着伤口愈合程序的表达，并在与炎症减轻相关的克罗恩病黏膜中发现了 CD161 T 细胞特征。这些发现确定了 CD161 T 细胞作为一种参与控制肠道中炎症和上皮屏障愈合之间平衡的群体。
