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

被引:13
作者
Huang, Saisai [1 ]
Wu, Shufang [2 ]
Zhang, Zhuoya [2 ]
Deng, Wei [2 ]
Fan, Junyu [3 ]
Feng, Ruihai [2 ]
Kong, Wei [2 ]
Qi, Jingjing [2 ]
Chen, Weiwei [2 ]
Tang, Xiaojun [2 ]
Yao, Genhong [2 ]
Feng, Xuebing [2 ]
Wang, Dandan [2 ]
Chen, Hongwei [2 ]
Sun, Lingyun [1 ]
机构
[1] Nanjing Med Univ, Dept Rheumatol & Immunol, Drum Tower Clin Med Coll, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China
[2] Nanjing Univ, Dept Rheumatol & Immunol, Affiliated Drum Tower Hosp, Med Sch, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China
[3] Nanjing Univ Chinese Med, Dept Rheumatol & Immunol, Nanjing Drum Tower Clin Med Coll Tradit Cinese &, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Mesenchymal stem cells; Apoptosis; Lupus mice; Lymphocytes; LYMPHOPROLIFERATIVE SYNDROME; FAS RECEPTOR; TRANSPLANTATION; NEPHRITIS; AUTOIMMUNITY; CLEARANCE; ROLES; DEATH; LPR;
D O I
10.1016/j.bbrc.2018.10.133
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x 10(6) human umbilical cordderived mesenchymal stem cells (UC-MSCs) were injected into B6.MRL-Fas(lPr) (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. (C) 2018 Published by Elsevier Inc.
引用
收藏
页码:30 / 35
页数:6
相关论文
共 34 条
[1]   Mesenchymal-Stem-Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis [J].
Akiyama, Kentaro ;
Chen, Chider ;
Wang, DanDan ;
Xu, Xingtian ;
Qu, Cunye ;
Yamaza, Takayoshi ;
Cai, Tao ;
Chen, WanJun ;
Sun, Lingyun ;
Shi, Songtao .
CELL STEM CELL, 2012, 10 (05) :544-555
[2]   Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages [J].
Choi, Hosoon ;
Lee, Ryang Hwa ;
Bazhanov, Nikolay ;
Oh, Joo Youn ;
Prockop, Darwin J. .
BLOOD, 2011, 118 (02) :330-338
[3]   THE LPR AND GLD GENES IN SYSTEMIC AUTOIMMUNITY - LIFE AND DEATH IN THE FAS LANE [J].
COHEN, PL ;
EISENBERG, RA .
IMMUNOLOGY TODAY, 1992, 13 (11) :427-428
[4]   Mesenchymal stem cells promote CD206 expression and phagocytic activity of macrophages through IL-6 in systemic lupus erythematosus [J].
Deng, Wei ;
Chen, Weiwei ;
Zhang, Zhuoya ;
Huang, Saisai ;
Kong, Wei ;
Sun, Yue ;
Tang, Xiaojun ;
Yao, Genhong ;
Feng, Xuebing ;
Chen, WanJun ;
Sun, Lingyun .
CLINICAL IMMUNOLOGY, 2015, 161 (02) :209-216
[5]   Mesenchymal Stem Cell: Keystone of the Hematopoietic Stem Cell Niche and a Stepping-Stone for Regenerative Medicine [J].
Frenette, Paul S. ;
Pinho, Sandra ;
Lucas, Daniel ;
Scheiermann, Christoph .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 31, 2013, 31 :285-316
[6]   The immunomodulatory capacity of mesenchymal stem cells [J].
Gebler, Antje ;
Zabel, Olivia ;
Seliger, Barbara .
TRENDS IN MOLECULAR MEDICINE, 2012, 18 (02) :128-134
[7]   Deletion of Receptor for Advanced Glycation End Products Exacerbates Lymphoproliferative Syndrome and Lupus Nephritis in B6-MRL Fas lpr/j Mice [J].
Goury, Antoine ;
Meghraoui-Kheddar, Aida ;
Belmokhtar, Karim ;
Vuiblet, Vincent ;
Ortillon, Jeremy ;
Jaisson, Stephane ;
Devy, Jerome ;
Le Naour, Richard ;
Tabary, Thierry ;
Cohen, Jacques H. M. ;
Schmidt, Ann-Marie ;
Rieu, Philippe ;
Toure, Fatouma .
JOURNAL OF IMMUNOLOGY, 2015, 194 (08) :3612-+
[8]   Differential effect of allogeneic versus syngeneic mesenchymal stem cell transplantation in MRL/lpr and (NZB/NZW)F1 mice [J].
Gu, Fei ;
Molano, Ivan ;
Ruiz, Philip ;
Sun, Lingyun ;
Gilkeson, Gary S. .
CLINICAL IMMUNOLOGY, 2012, 145 (02) :142-152
[9]   Different roles of PD-L1 and FasL in immunomodulation mediated by human placenta-derived mesenchymal stem cells [J].
Gu, Yan-zheng ;
Xue, Qun ;
Chen, Yong-jing ;
Yu, Ge-Hua ;
Qing, Ming-de ;
Shen, Yu ;
Wang, Ming-yuan ;
Shi, Qin ;
Zhang, Xue-Guang .
HUMAN IMMUNOLOGY, 2013, 74 (03) :267-276
[10]   THE POLYPEPTIDE ENCODED BY THE CDNA FOR HUMAN CELL-SURFACE ANTIGEN FAS CAN MEDIATE APOPTOSIS [J].
ITOH, N ;
YONEHARA, S ;
ISHII, A ;
YONEHARA, M ;
MIZUSHIMA, S ;
SAMESHIMA, M ;
HASE, A ;
SETO, Y ;
NAGATA, S .
CELL, 1991, 66 (02) :233-243