Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs.
Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs.
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DOI：
10.1186/s13287-022-03002-y
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发表时间：
2022-07-18
影响因子：
7.5
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中科院分区：
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间充质干细胞(MSC)移植减轻系统性红斑狼疮(SLE)动脉粥样硬化的机制仍不清楚。本研究旨在探讨骨髓基质细胞改善系统性红斑狼疮动脉粥样硬化的疗效及机制。将B6背景的apoE−/−小鼠和Fas−/−小鼠杂交，建立动脉粥样硬化的系统性红斑狼疮小鼠。对髓系抑制细胞(MDSCs)进行分类和定量。用抗Gr抗体处理apoE−/−Fas−/−小鼠或注射MDSCs。对狼疮样自身免疫和动脉粥样硬化病变进行评估。此外，将载脂蛋白E−/−Fas−/−小鼠移植入骨髓间充质干细胞，观察狼疮样自身免疫和动脉粥样硬化病变情况。载脂蛋白E−/−Fas−/−小鼠外周血、脾、引流淋巴结中的MDSCs较B6小鼠增多。此外，过继转移MDSCs加重了动脉粥样硬化和系统性红斑狼疮的病理，而耗尽MDSCs则改善了apoE−/−Fas−/−小鼠的这些病理变化。骨髓间充质干细胞移植于载脂蛋白E−/−Fas−/−小鼠体内可降低骨髓间充质干细胞的比例，减轻典型的动脉粥样硬化病变，包括主动脉和肝脏的动脉硬化病变，并降低血清胆固醇、甘油三酯和低密度脂蛋白水平。骨髓间充质干细胞移植还减少了SLE的病理改变，包括脾肿大、肾小球病变、血清抗dsDNA抗体、尿蛋白和血肌酐。此外，骨髓间充质干细胞移植通过分泌前列腺素E2(PGE2)来调节MDSCs的生成和功能。综上所述，这些结果表明MDSCs的增加参与了SLE的动脉粥样硬化。骨髓间充质干细胞移植通过分泌PGE2减少MDSCs，从而改善动脉粥样硬化和系统性红斑狼疮。网上版载有补充材料，可在10.1186/s13287-022-03002-y查阅。
The mechanism by which mesenchymal stem cell (MSC) transplantation alleviates atherosclerosis in systemic lupus erythematosus (SLE) remains elusive. In this study, we aim to explore the efficacy and mechanism of MSC in ameliorating atherosclerosis in SLE. ApoE−/− and Fas−/− mice on the B6 background were cross-bred to generate SLE mice with atherosclerosis. Myeloid-derived suppressor cells (MDSCs) were sorted and quantified. The apoE−/−Fas−/− mice were either treated with anti-Gr antibody or injected with MDSCs. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. Furthermore, the apoE−/−Fas−/− mice were transplanted with MSCs and lupus-like autoimmunity and atherosclerotic lesions were assessed. MDSCs in peripheral blood, spleen, draining lymph nodes increased in apoE−/−Fas−/− mice compared with B6 mice. Moreover, the adoptive transfer of MDSCs aggravated both atherosclerosis and SLE pathologies, whereas depleting MDSCs ameliorated those pathologies in apoE−/−Fas−/− mice. MSC transplantation in apoE−/−Fas−/− mice decreased the percentage of MDSCs, alleviated the typical atherosclerotic lesions, including atherosclerotic lesions in aortae and liver, and reduced serum cholesterol, triglyceride and low-density lipoprotein levels. MSC transplantation also reduced SLE pathologies, including splenomegaly, glomerular lesions, anti-dsDNA antibody in serum, urine protein and serum creatinine. Moreover, MSC transplantation regulated the generation and function of MDSCs through secreting prostaglandin E 2 (PGE2). Taken together, these results indicated that the increased MDSCs contributed to atherosclerosis in SLE. MSC transplantation ameliorated the atherosclerosis and SLE through reducing MDSCs by secreting PGE2. The online version contains supplementary material available at 10.1186/s13287-022-03002-y.
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