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间充质干细胞诱导 CD4+T 细胞凋亡治疗狼疮小鼠。

Mesenchymal stem cells induced CD4+ T cell apoptosis in treatment of lupus mice.

机构信息

Department of Rheumatology and Immunology, Drum Tower Clinical Medical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.

Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.

出版信息

Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):30-35. doi: 10.1016/j.bbrc.2018.10.133. Epub 2018 Nov 5.

DOI:10.1016/j.bbrc.2018.10.133
PMID:30409422
Abstract

Umbilical cord-derived mesenchymal stem cell transplantation (UCMSCT) has been used to treat human autoimmune diseases like lupus for example, but little is known about its effect on cell apoptosis. Here we evaluated the efficacy of UCMSCT for lupus treatment and explored the mechanism by which mesenchymal stem cells (MSCs) modulate T cell apoptosis in lupus mice. 1 × 10 human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were injected into B6.MRL-Fas (B6.lpr) mice via tail vein. 6 h, 24 h or 4 weeks later, the mice were sacrificed and the apoptosis of lymphocytes in peripheral blood and spleen were detected by flow cytometry. The immune cell subpopulations in spleen were also measured at 6 h and 24 h, respectively. The therapeutic effects were assessed after 4 weeks. The frequency of peripheral blood CD4+ T cell apoptosis was reduced in lupus-prone B6.lpr mice. UCMSCT alleviated the disease phenotypes in B6.lpr mice, decreased the ratio of Th1 as well as Th2 cells, and increased percentages of apoptotic CD4+ T cells in vivo and vitro. Collectively, our findings unravel that UCMSCT alleviate lupus disease and reverse immune imbalance possibly by promoting T cell apoptosis in B6.lpr mice.

摘要

脐带间充质干细胞移植(UCMSCT)已被用于治疗人类自身免疫性疾病,例如狼疮,但对于其对细胞凋亡的影响知之甚少。在这里,我们评估了 UCMSCT 治疗狼疮的疗效,并探讨了间充质干细胞(MSCs)在狼疮小鼠中调节 T 细胞凋亡的机制。通过尾静脉向 B6.MRL-Fas(B6.lpr)小鼠注射 1×10 个人类脐带间充质干细胞(UC-MSCs)。6 h、24 h 或 4 周后,通过流式细胞术检测外周血和脾脏中淋巴细胞的凋亡情况。分别在 6 h 和 24 h 时测量脾脏中的免疫细胞亚群。4 周后评估治疗效果。狼疮易感 B6.lpr 小鼠外周血 CD4+T 细胞凋亡的频率降低。UCMSCT 减轻了 B6.lpr 小鼠的疾病表型,降低了 Th1 和 Th2 细胞的比例,并增加了体内和体外凋亡 CD4+T 细胞的百分比。总之,我们的研究结果表明,UCMSCT 通过促进 B6.lpr 小鼠 T 细胞凋亡来缓解狼疮疾病和逆转免疫失衡。

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