CCR2 is expressed by tendon resident macrophage and T cells, while CCR2 deficiency impairs tendon healing via blunted involvement of tendon-resident and circulating monocytes/macrophages.
CCR2 is expressed by tendon resident macrophage and T cells, while CCR2 deficiency impairs tendon healing via blunted involvement of tendon-resident and circulating monocytes/macrophages.
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DOI：
10.1096/fj.202201162r
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发表时间：
2022-11
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在肌腱愈合过程中，巨噬细胞被认为是瘢痕组织形成的关键介质，其阻止肌腱的成功功能恢复。然而，巨噬细胞对于成功的肌腱愈合至关重要，因为它们有助于伤口清创、细胞外基质沉积并促进成纤维细胞增殖。最近的工作试图更好地定义多方面的功能，巨噬细胞使用消耗研究，而其他研究已经确定了肌腱居民巨噬细胞群体。为了开始描述肌腱驻留与循环来源的巨噬细胞的功能，我们检查了趋化因子受体2（CCR 2）报告基因（CCR 2 GFP/+）和基因敲除小鼠的肌腱愈合表型。CCR 2是主要在循环的骨髓来源的单核细胞的表面上发现的趋化因子受体，其中CCR 2是巨噬细胞募集到伤口环境的重要介质。令人惊讶的是，CCR 2GFP/+细胞在成人体内平衡期间存在于肌腱中，单细胞RNA测序将这些细胞鉴定为肌腱驻留巨噬细胞和T细胞。在稳态和愈合期间，CCR 2敲除导致CCR 2GFP+细胞和泛巨噬细胞的大幅减少。此外，CCR 2的缺失导致肌成纤维细胞数量减少，并阻碍了晚期愈合期间的功能恢复。这项研究强调了肌腱驻留和招募的免疫细胞的异质性及其在损伤后的贡献，并确定了CCR 2在调节成人肌腱细胞环境和肌腱愈合过程中的重要作用。
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 (CCR2GFP/+), 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, CCR2GFP/+ 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 CCR2GFP+ 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.