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一种离散的"早期响应"状细胞亚型协调免疫细胞招募到受伤组织中

Omar K Yaghi^1,2, Bola S Hanna^1,2, P Kent Langston^1,2

¹Department of Immunology, Harvard Medical School, Boston, MA, USA.

Nature immunology

|November 6, 2023

概括

肌肉 stromal 细胞作为早期响应损伤,启动炎症和协调免疫细胞活动用于组织修复. 这些细胞通过单细胞RNA测序识别,在再生过程中起着至关重要的作用.

科学领域:

再生医学是一种再生医学.
免疫学免疫学免疫学
细胞生物学细胞生物学

背景情况:

众所周知,通过各种机制,肌体细胞通过各种机制在受伤后促进组织再生.
了解急性损伤反应期间肌细胞的特定亚型和功能,对于开发向疗法至关重要.

研究的目的:

识别和描述响应急性损伤的特定亚型的肌肉介质干细胞 (MmSCs).
阐明受伤诱导炎症和再生的早期阶段所涉及的分子机制和细胞相互作用.

主要方法:

时间解析的单细胞RNA测序用于分析急性肌肉损伤后的MMSCs.
进行了体内细胞转移实验,以评估已识别的MmmSC亚型的炎症潜力.
进行了化学基因耗尽研究,以评估特定的炎症媒介,如Cxcl5,在中性粒细胞招募和再生中的作用.

主要成果:

确定了一种"早期响应"的MMSC亚型,其特征是受伤时免疫调节转录的快速表达.
发现像IL-1β,TNF-α和oncostatin M这样的关键炎症细胞因子能够在MMSC中快速诱导这种免疫调节程序.
这种炎症性MmSC亚型的转移诱导了中性粒细胞和巨细胞驱动的炎症,Cxcl5被确定为中性粒细胞招募的关键性流体特异化基因.
耗尽Cxcl5损害了中性粒细胞的招募,延长了炎症和受影响的组织再生.
在肌肉衰竭模型和其他人类和小鼠病理中观察到类似的炎症性MMSC程序.

结论:

"早期响应"的MMSCs对于急性损伤后炎症反应的快速启动和放大至关重要.
这些细胞协调免疫细胞的招募和激活,如中性粒细胞和巨细胞,对于组织修复至关重要.
这些发现突出了针对MMSC衍生的炎症程序和Cxcl5等化学激素的治疗潜力,以增强组织再生和管理炎症状况.

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