Human umbilical cord mesenchymal stem cells derived extracellular vesicles regulate acquired immune response of lupus mouse in vitro

被引:15
作者
Xie, Min [1 ]
Li, Cuifang [1 ]
She, Zhou [1 ]
Wu, Feifeng [1 ]
Mao, Jueyi [1 ]
Hun, Marady [1 ]
Luo, Senlin [1 ]
Wan, Wuqing [1 ]
Tian, Jidong [1 ]
Wen, Chuan [1 ]
机构
[1] Cent South Univ, Xiangya Hosp 2, Div Hematol & Tumor, Childrens Med Ctr, Changsha, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
FOLLICULAR HELPER-CELL; AUTOIMMUNE-DISEASES; STROMAL CELLS; TRANSPLANTATION; INTERLEUKIN-10; ERYTHEMATOSUS; MRL/LPR; RECEPTOR; BLOOD; DIFFERENTIATION;
D O I
10.1038/s41598-022-17331-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Immunopathology believes that abnormal T cell function and excessive production of autoantibodies by B cells are involved in multi-organ damage. Human umbilical cord mesenchymal stem cells (hUCMSCs) therapies have endowed with promise in SLE, while the function of MSC-derived extracellular vesicles (MSC-EVs) was still unclear. Extracellular vesicles (EVs) are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles. EVs play a vital role in cell-to-cell communication by acting as biological transporters. New evidence has shown beneficial effects of MSC-EVs on autoimmune diseases, such as their immunomodulatory properties. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE. We isolated splenic mononuclear cells from MRL/lpr mice, a classical animal model of SLE. PBS (Phosphate-buffered saline), 2 x 10(5) hUCMSCs, 25 mu g/ml hUCMSC-EVs, 50 mu g/ml hUCMSC-EVs were co-cultured with 2 x 10(6) activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4(+) T cell subsets, B cells and the concentrations of cytokines were detected. Both hUCMSCs and hUCMSC-EVs inhibited CD4(+) T cells, increased the production of T helper (Th)17 cells, promoted the production of interleukin (IL)-17 and transforming growth factor beta1 (TGF-beta 1) (P < 0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg) cells and IL-10 (P > 0.05); only hUCMSCs inhibited CD19(+) B cells, promoted the production of interferon-gamma (IFN-gamma) and IL-4 (P < 0.05). hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, therefore, hUCMSC-EVs play novel and potential regulator roles in SLE.
引用
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页数:9
相关论文
共 52 条
[31]   Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used [J].
Loh, Yvonne ;
Oyama, Yu ;
Statkute, Laisvyde ;
Quigley, Kathleen ;
Yaung, Kimberly ;
Gonda, Elizabeth ;
Barr, Walter ;
Jovanovic, Borko ;
Craig, Robert ;
Stefoski, Dusan ;
Cohen, Bruce ;
Burt, Richard K. .
BLOOD, 2007, 109 (06) :2643-2648
[32]  
Nurudhin A, 2017, BANGLADESH J MED SCI, V16, P418, DOI 10.3329/bjms.v16i3.32862
[33]  
Ohtsuka K, 1998, J IMMUNOL, V160, P2539
[34]   Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus [J].
Peng, Hui ;
Wang, Wei ;
Zhou, Mo ;
Li, Rui ;
Pan, Hai-Feng ;
Ye, Dong-Qing .
CLINICAL RHEUMATOLOGY, 2013, 32 (09) :1255-1266
[35]   Murine Models of Systemic Lupus Erythematosus [J].
Perry, Daniel ;
Sang, Allison ;
Yin, Yiming ;
Zheng, Ying-Yi ;
Morel, Laurence .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2011,
[36]   Marrow stromal cells as steam cells for nonhematopoietic tissues [J].
Prockop, DJ .
SCIENCE, 1997, 276 (5309) :71-74
[37]   Use of genetic knockouts to modulate disease expression in a murine model of lupus, MRL/lpr mice [J].
Reilly, CM ;
Gilkeson, GS .
IMMUNOLOGIC RESEARCH, 2002, 25 (02) :143-153
[38]   Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients [J].
Ren, S. ;
Hu, J. ;
Chen, Y. ;
Yuan, T. ;
Hu, H. ;
Li, S. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2016, 183 (03) :389-396
[39]   INTERLEUKIN-10 IS A POTENT GROWTH AND DIFFERENTIATION FACTOR FOR ACTIVATED HUMAN LYMPHOCYTES-B [J].
ROUSSET, F ;
GARCIA, E ;
DEFRANCE, T ;
PERONNE, C ;
VEZZIO, N ;
HSU, DH ;
KASTELEIN, R ;
MOORE, KW ;
BANCHEREAU, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) :1890-1893
[40]   New Technologies for Analysis of Extracellular Vesicles [J].
Shao, Huilin ;
Im, Hyungsoon ;
Castro, Cesar M. ;
Breakefield, Xandra ;
Weissleder, Ralph ;
Lee, Hakho .
CHEMICAL REVIEWS, 2018, 118 (04) :1917-1950