title: Amelioration of myocarditis by HVEM-overexpressing dendritic cells through induction of IL-10-producing cells.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Experimental Diagnosis, Shanghai Changhai Hospital, Shanghai 200433, People's Republic of China.
authors: Gang
authors: G
authors: Cai
authors: Huaizhou
authors: H
authors: Wang
authors: Qin
authors: Q
authors: Qin
authors: Jun
authors: J
authors: Zhang
authors: Zhi
authors: Z
authors: Zhu
authors: Menglei
authors: M
authors: Liu
authors: Qian
authors: Q
authors: Shen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009218:Myosins; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D053240:Receptors, Tumor Necrosis Factor, Member 14; C506029:Tnfrsf14 protein, mouse; D016753:Interleukin-10; D009218:Myosins