期刊
FASEB JOURNAL
卷 36, 期 11, 页码 -出版社
WILEY
DOI: 10.1096/fj.202201162R
关键词
CCR2; fibrosis; macrophage; myofibroblast; tendon healing
资金
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R01 AR077527, R01AR073169, T32 AR076950, K99 AR080757, P30AR069655]
Macrophages play a complex role in tendon healing, with both positive and negative effects on the process. This study identified the presence of tendon-resident macrophages and T cells during both homeostasis and healing. Furthermore, it demonstrated the importance of CCR2 in modulating the tendon cell environment and promoting functional recovery during late healing.
During tendon healing, macrophages are thought to be a key mediator of scar tissue formation, which prevents successful functional restoration of the tendon. However, macrophages are critical for successful tendon healing as they aid in wound debridement, extracellular matrix deposition, and promote fibroblast proliferation. Recent work has sought to better define the multi-faceted functions of macrophages using depletion studies, while other studies have identified a tendon resident macrophage population. To begin to delineate the functions of tendon-resident versus circulation-derived macrophages, we examined the tendon healing phenotype in Chemokine Receptor 2 (CCR2) reporter (CCR2(GFP/+)), and knockout mice. CCR2 is a chemokine receptor primarily found on the surface of circulating bone marrow-derived monocytes, with CCR2 being an important mediator of macrophage recruitment to wound environments. Surprisingly, CCR2(GFP/+) cells were present in the tendon during adult homeostasis, and single-cell RNA sequencing identified these cells as tendon-resident macrophages and T cells. During both homeostasis and healing, CCR2 knockout resulted in a substantial decrease in CCR2(GFP+) cells and pan-macrophages. Additionally, loss of CCR2 resulted in reduced numbers of myofibroblasts and impeded functional recovery during late healing. This study highlights the heterogeneity of tendon-resident and recruited immune cells and their contributions following injury, and establishes an important role for CCR2 in modulating both the adult tendon cell environment and tendon healing process.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据