Extracellular vesicles derived from mesenchymal stem cells prevent skin fibrosis in the cGVHD mouse model by suppressing the activation of macrophages and B cells immune response
Extracellular vesicles derived from mesenchymal stem cells prevent skin fibrosis in the cGVHD mouse model by suppressing the activation of macrophages and B cells immune response
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间充质干细胞来源的细胞外囊泡通过抑制巨噬细胞和 B 细胞免疫反应的激活来预防 cGVHD 小鼠模型中的皮肤纤维化
DOI：
10.1016/j.intimp.2020.106541
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发表时间：
2020-07-01
影响因子：
5.6
通讯作者：
Weng, Jianyu
中科院分区：
文献类型：
--
作者：
Guo, Liyan;Lai, Peilong;Weng, Jianyu
目的：探讨间充质干细胞（msc - ev）细胞外囊泡对同种异体造血干细胞移植后硬皮病慢性移植物抗宿主病（cGVHD）模型纤维化的潜在影响及其机制。方法：我们首先观察msc - ev对小组织相容性单倍相同的硬皮病cGVHD模型的治疗作用，以及msc - ev对皮肤纤维化和巨噬细胞活化及相关促纤维化蛋白的作用。此外，我们在体内观察了msc - ev对B细胞、T滤泡辅助细胞（TFH）和生发中心B细胞（GC B细胞）相互作用的影响以及B细胞活化因子（BAFF）与B细胞的比例。结果：msc - ev治疗可减轻硬化性cGVHD小鼠的cGVHD评分和皮肤纤维化，这与皮肤和脾脏巨噬细胞百分比降低、皮肤巨噬细胞浸润减少、tgf - β和smad2生成减少有关。此外，msc - ev在体内通过阻断TFH/GC B细胞相互作用和降低BAFF与B细胞的比例来影响B细胞的免疫应答。结论：MSC-EVs通过抑制巨噬细胞活化和B细胞免疫应答来预防硬化性皮肤cGVHD小鼠模型纤维化。
Objective: To illustrate the potential effects and mechanism of extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) on fibrosis in sclerodermatous chronic graft-versus-host-disease (cGVHD) models after allogeneic hematopoietic stem cell transplantation.Methods: We first observed the therapeutic effects of MSC-EVs on a minor histocompatibility haploidentical model of sclerodermatous cGVHD and the function of MSC-EVs on skin fibrosis and macrophage activation and the related pro-fibrosis protein. Additionally, we observed the effects of MSC-EVs on B cells, the T follicular helper cell (TFH) and germinal center B cell (GC B cells) interaction and the ratio of B cell activation factor (BAFF) to B cells in vivo.Results: MSC-EVs treatment could alleviate the cGVHD scores and fibrosis of skin in sclerodermatous cGVHD mice, and this was associated with a reduction macrophage percentage in the skin and spleen, and a reduction in macrophage infiltration and TGF-beta and smad2 production in the skin. Additionally, MSC-EVs influence B cells immune response by blocking the TFH/GC B cells interaction and reducing the ratio of BAFF to B cells in vivo.Conclusion: MSC-EVs prevent the fibrosis of sclerodermatous cGVHD mouse model by suppressing the activation of macrophages and B cells immune response.