目的: 研究脐带间充质干细胞(UC-MSCs)对干燥综合征(SS)患者外周血的免疫调节作用。方法: 取新生儿脐带组织分离并培养UC-MSCs,流式细胞术检测UC-MSCs的细胞表面标记;选取20例疾病活动期的SS患者,收集静脉血提取外周血单个核细胞(PBMC),将SS患者的PBMC与UC-MSCs共培养,CCK-8法检测细胞存活率,筛选最优共培养细胞比例进行后续实验;流式细胞术检测共培养后SS患者PBMC中淋巴细胞亚群的变化情况。结果: UC-MSCs可降低SS患者PBMC中的外周血CD3+ T细胞、CD3+CD8+ T细胞以及CD19+ B细胞的比例,而CD16+ CD56+ NK细胞比例、CD3+ CD4+ T细胞比例、CD4+ /CD8+ 无明显变化。结论: UC-MSCs可以调节SS患者的免疫功能,从而对SS有一定的治疗作用。
Objective: To study the immunoregulatory effect of umbilical cord mesenchymal stem cells (UC-MSCs) on peripheral blood of patients with Sjogren's syndrome (SS). Methods: UC-MSCs were isolated and cultured from umbilical cord tissue of newborns, and the cell surface markers of UC-MSCs were detected by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were collected from 20 SS patients in the active phase of the disease. Co-cultures of PBMCs from SS patients with UC-MSCs were established, and cell viability was assessed using the CCK-8 assay. The optimal ratio of co-cultured cells was determined for subsequent experiments. Flow cytometry was used to analyze the changes in lymphocyte subsets in SS patient PBMCs after co-culture. Results: UC-MSCs reduced the proportions of peripheral blood CD3+ T cells, CD3+ CD8+ T cells, and CD19+ B cells in PBMC of SS patients, while the proportions of CD16+ CD56+ NK cells, CD3+ CD4+ T cells, and CD4+ /CD8+ ratio were not significantly affected. Conclusion: UC-MSCs can modulate the immune function of SS patients, thereby exerting a certain therapeutic effect on SS.
[1] Tian Y, Yang HY, Liu N. Advances in pathogenesis of Sjögren's syndrome[J]. J Immunol Res,2021, 2021:5928232.
[2] Shen L, He J, Kramer JM, et al. Sjögren's syndrome: animal models, etiology, pathogenesis, clinical subtypes, and diagnosis [J]. J Immunol Res, 2019, 2019: 8101503.
[3] Goules AV, Kapsogeorgou EK, Tzioufas AG. Insight into pathogenesis of Sjögren's syndrome: Dissection on autoimmune infiltrates and epithelial cells [J]. Clin Immunol,2017, 182:30-40.
[4] Li N, Hua J. Interactions between mesenchymal stem cells and the immune system [J]. Cell Mol Life Sci, 2017, 74(13): 2345-2360.
[5] Ben-Ami E, Berrih-Aknin S, Miller A. Mesenchymal stem cells as an immunomodulatory therapeutic strategy for autoimmune diseases [J]. Autoimmun Rev, 2011, 10(7): 410-415.
[6] Xu J, Wang D, Liu D, et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren's syndrome [J]. Blood, 2012, 120(15): 3142-3151.
[7] Fiona André, Barbara C Böckle. Sjögren's syndrome[J].J Immunol Res,2022, 20(7): 980-1002.
[8] Verstappen Gwenny M,Kroese Frans GM,Bootsma Hendrika. T cells in primary Sjögren's syndrome: targets for early intervention[J] .Rheumatology (Oxford), 2019, 60:3088-3098.
[9] Yoko Ogawa, Tsutomu Takeuchi, Kazuo Tsubota. Autoimmune epithelitis and chronic inflammation in sjögren's syndrome-related dry eye disease[J]. Int J Mol Sci, 2021, 22(21): 11820.
[10] 李学平. 干燥综合征患者外周血T淋巴细胞亚群及Th类细胞因子表达的变化观察[J].中国医学创新,2021,18(16):117-120.
[11] Liu Y, Li C, Wang S, et al. Human umbilical cord mesenchymal stem cells confer potent immunosuppressive effects in Sjögren's syndrome by inducing regulatory T cells [J]. Mod Rheumatol, 2021, 31(1): 186-196.
[12] Rivière E, Pascaud J, Tchitchek N, et al. Salivary gland epithelial cells from patients with Sjögren's syndrome induce B-lymphocyte survival and activation [J]. Ann Rheum Dis, 2020, 79(11): 1468-1477.
[13] Du WH, Han M, Zhu XX. The Multiple roles of B cells in the pathogenesis of Sjögren's syndrome[J]. Front Immunol, 2021, 12: 684999.
[14] El-jawhari JJ, El-sherbiny YM, Jones EA, et al. Mesenchymal stem cells, autoimmunity and rheumatoid arthritis [J]. Qjm, 2014, 107(7): 505-514.
[15] Fayhollahi A, Gabalou NB, Aslani S. Mesenchymal stem cell transplantation in systemic lupus erythematous, a mesenchymal stem cell disorder [J]. Lupus, 2018, 27(7): 1053-1064.
