Aorta Regulatory T Cells with a Tissue‐Specific Phenotype and Function Promote Tissue Repair through Tff1 in Abdominal Aortic Aneurysms
Jingyong Li, Ni Xia, Dan Li, Shuang Wen, Shirui Qian, Yuzhi Lu, Muyang Gu, Tingting Tang, Jiao Jiao, Bingjie Lv, Shaofang Nie, Desheng Hu, Yuhua Liao, Xiang‐Ping Yang, Guo‐Ping Shi, Xiang Cheng
Abstract
Abstract In addition to maintaining immune tolerance, Foxp3 + regulatory T cells (Tregs) perform specialized functions in tissue homeostasis and remodeling. However, whether Tregs in aortic aneurysms have a tissue‐specific phenotype and function is unclear. Here, a special group of Tregs that potentially inhibit abdominal aortic aneurysm (AAA) progression are identified and functionally characterized. Aortic Tregs gradually increase during the process of AAA and are mainly recruited from peripheral circulation. Single‐cell TCR sequencing and bulk RNA sequencing demonstrate their unique phenotype and highly expressed trefoil factor 1 (Tff1). Foxp3 cre/cre Tff1 flox/flox mice are used to clarify the role of Tff1 in AAA, suggesting that aortic Tregs secrete Tff1 to regulate smooth muscle cell (SMC) survival. In vitro experiments confirm that Tff1 inhibits SMC apoptosis through the extracellular signal‐regulated kinase (ERK) 1/2 pathway. The findings reveal a tissue‐specific phenotype and function of aortic Tregs and may provide a promising and novel approach for the prevention of AAA.