Quantitative analysis of immune cell subset infiltration of supraspinatus muscle after severe rotator cuff injury.
Quantitative analysis of immune cell subset infiltration of supraspinatus muscle after severe rotator cuff injury.
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DOI：
10.1007/s40883-017-0030-2
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发表时间：
2017-06
影响因子：
2.6
通讯作者：
Botchwey EA
中科院分区：
文献类型：
--
作者：
Krieger JR;Tellier LE;Ollukaren MT;Temenoff JS;Botchwey EA
肩袖撕裂导致肌肉退化，以肌纤维萎缩、脂肪渗透和纤维化为特征，对目前的治疗方案反应最小。肩袖肌肉退行性变的潜在发病机制尚不清楚，越来越多的证据表明免疫细胞的渗透是一个重要因素。由于免疫细胞由高度不同的亚群组成，这些亚群对损伤组织产生不同的影响，了解免疫亚群的运输和积累可能是更有效治疗的关键。本研究量化了严重肩袖损伤(包括肌腱切断和失神经)后小鼠冈上肌中免疫细胞的亚群。肩袖损伤刺激单核巨噬细胞的显著渗透，在非经典亚群中丰富单核巨噬细胞，在TH和Treg亚群中丰富T淋巴细胞。与单纯肌腱切断术相比，肌腱切断加去神经支配显著增加了单核巨噬细胞的浸润，丰富了非经典亚群中的巨噬细胞，减少了T淋巴细胞在TH细胞中的聚集。肌腱切断术和去神经后，通过脂质体消耗循环单核细胞加速冈上肌萎缩。这项研究可能有助于合理设计免疫智能疗法，利用免疫细胞来改善肩袖撕裂后的预后。
Rotator cuff tears cause muscle degeneration that is characterized by myofiber atrophy, fatty infiltration, and fibrosis and is minimally responsive to current treatment options. The underlying pathogenesis of rotator cuff muscle degeneration remains to be elucidated, and increasing evidence implicates immune cell infiltration as a significant factor. Because immune cells are comprised of highly heterogeneous subpopulations that exert divergent effects on injured tissue, understanding trafficking and accumulation of immune subpopulations may hold the key to more effective therapies. The present study quantifies subpopulations of immune cells infiltrating the murine supraspinatus muscle after severe rotator cuff injury that includes tenotomy and denervation. Rotator cuff injury stimulates dramatic infiltration of mononuclear phagocytes, enriches mononuclear phagocytes in non-classical subpopulations, and enriches T lymphocytes in TH and Treg subpopulations. The combination of tenotomy plus denervation significantly increases mononuclear phagocyte infiltration, enriches macrophages in the non-classical subpopulation, and decreases T lymphocyte enrichment in TH cells compared to tenotomy alone. Depletion of circulating monocytes via liposomal clodronate accelerates supraspinatus atrophy after tenotomy and denervation. The study may aid rational design of immunologically smart therapies that harness immune cells to enhance outcomes after rotator cuff tears.