Cardiovascular Research Advance Access [Accepted Manuscript] published online on July 1, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp219
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Amelioration of myocarditis by HVEM-overexpressing dendritic cells through induction of IL-10-producing cells
1 Department of Experimental Diagnosis; Shanghai Changhai Hospital,
2 Department of Pathology; Shanghai Changhai Hospital
Address correspondence and reprint requests to Qian Shen, Department of Experimental Diagnosis, Shanghai Changhai Hospital, 168# Changhai road, Shanghai 200433, P. R. China. Telephone: (86) 021-8187 3611; Fax: (86) 021-8187 3611; Email: laoshenqch{at}yahoo.cn
Aims: 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.
Methods: 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.
Results: DCs transfected with AdHVEM (DC-AdHVEM) were protected against EAM, while HVEM-Ig had no protective effect. Further study showed 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.
KEYWORDS Experimental Autoimmune Myocarditis; Herpes Virus Entry Mediator; Immune Regulation; Dendritic Cells, IL-10
Time for primary review: 35 Days