A distinct“repair”role of regulatory T cells in fracture healing  

作　　者：Tingting Wu Lulu Wang Chen Jian Zhenhe Zhang Ruiyin Zeng Bobin Mi Guohui Liu Yu Zhang Chen Shi 

机构地区：[1]Department of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China [2]Hubei Province Clinical Research Center for Precision Medicine for Critical Illness,Wuhan,430022,China [3]Department of Orthopedics,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China

出　　处：《Frontiers of Medicine》2024年第3期516-537,共22页医学前沿（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.82274026 and 81901884).

摘　　要：Regulatory T cells(Tregs)suppress immune responses and inflammation.Here,we described the distinct nonimmunological role of Tregs in fracture healing.The recruitment from the circulation pool,peripheral induction,and local expansion rapidly enriched Tregs in the injured bone.The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs.Punctual depletion of Tregs compromised the fracture healing process,which leads to increased bone nonunion.In addition,bone callus Tregs showed unique T-cell receptor repertoires.Amphiregulin was the most overexpressed protein in bone callus Tregs,and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways.The results of loss-and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction.Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells.Our findings indicate the distinct and nonredundant role of Tregs in fracture healing,which will provide a new therapeutic target and strategy in the clinical treatment of fractures.

关 键 词：regulatory T cells fracture healing AMPHIREGULIN NON-UNION OSTEOGENESIS 

分 类 号：R68[医药卫生—骨科学]