Amelioration of myocarditis by HVEM-overexpressing dendritic cells through induction of IL-10-producing cells

被引:17
作者
Cai, Gang [1 ]
Wang, Huaizhou [1 ]
Qin, Qin [1 ]
Zhang, Jun [1 ]
Zhu, Zhi [2 ]
Liu, Menglei [1 ]
Shen, Qian [1 ]
机构
[1] Shanghai Changhai Hosp, Dept Expt Diag, Shanghai 200433, Peoples R China
[2] Shanghai Changhai Hosp, Dept Pathol, Shanghai 200433, Peoples R China
关键词
Experimental autoimmune myocarditis; Herpes virus entry mediator; Immune regulation; Dendritic cells; IL-10; HERPESVIRUS ENTRY MEDIATOR; EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; T-LYMPHOCYTE ATTENUATOR; B-LYMPHOCYTE; ACTIVATION; BTLA; INHIBITION; RECEPTOR;
D O I
10.1093/cvr/cvp219
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Herpes virus entry mediator (HVEM) is considered to be a molecular 'switch' for immune responses, and a role in immune modification has been reported. The aim of this study was to assess whether HVEM-mediated immune suppression could protect against experimental autoimmune myocarditis (EAM) induced by myosin. We constructed HVEM-expressing adenovirus (AdHVEM) and fusion protein HVEM-Ig and evaluated their roles in immunoregulation in vitro and in vivo. Immunoregulation of dendritic cells (DCs) infected with recombinant virus or treated with HVEM-Ig was then studied. DCs transfected with AdHVEM (DC-AdHVEM) were protected against EAM, whereas HVEM-Ig had no protective effect. Further study showed that DC-AdHVEMs produced a regulatory cytokine, IL-10, which had further effects on induction of IL-10 producing CD4(+) T cells. This subset of T cells was then responsible for the protection against EAM. Myosin-DC-AdHVEM cell gene therapy appears to be a safe and effective way of inhibiting the development of EAM. The signal induced by HVEM seems to play different roles in different cells.
引用
收藏
页码:425 / 433
页数:9
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