Adoptive Transfer of Regulatory T Cells Protects against Coxsackievirus B3-Induced Cardiac Fibrosis
Open Access
- 4 September 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (9), e74955
- https://doi.org/10.1371/journal.pone.0074955
Abstract
Cardiac fibrogenesis in the late stage of viral myocarditis causing contractile dysfunction and ventricular dilatation, is a major pathogenic factor for the progression of myocarditis to serious cardiovascular diseases including dilated cardiomyopathy (DCM) and congestive heart failure (HF). Recent studies indicate that regulatory T cells (Tregs) are involved in the fibrotic process of liver and lung fibosis. However, the role of Tregs in the development of viral myocarditis-caused cardiac fibrosis and their therapeutic potential remains unclear. Myocardial fibrosis was induced in BALB/c mice by intraperitoneal injection of Coxsackievirus B3 (CVB3) assessed by picrosirius red staining and detection of expression levels of collagen I, matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Myocardial Treg frequency was down-regulated during the course of viral myocarditis and a negative correlation with the severity of cardiac fibrosis was found. To explore the role of Tregs in CVB-induced cardiac fibrosis, Treg was in vivo depleted by injecting anti-CD25 mAb which resulted in aggravation of cardiac fibrosis. In consistent with that, after adoptive transfer of isolated Tregs into mice, significant amelioration of CVB3-induced cardiac fibrosis was confirmed. Interleukin-10 (IL-10) neutralizing antibodies were used in vivo and in vitro to explore the molecular mechanism of the therapeutic effect of Treg. It was found that administration of anti-IL-10 mAb after Treg transfer abrogated Treg’s treating effect and the inhibition of Treg on collagen production by cardiac fibroblasts was mediated mainly through IL-10. Our data suggested that Tregs have a protective role in the fibrotic process of CVB3-induced cardiac fibrosis via secreting IL-10 and might provide an alternative option for the future treatment of cardiac fibrosis.Keywords
This publication has 38 references indexed in Scilit:
- The plasticity and stability of regulatory T cellsNature Reviews Immunology, 2013
- Molecular basis of organ fibrosis: Potential therapeutic approachesExperimental Biology and Medicine, 2013
- IL-10 Treatment Is Associated with Prohibitin Expression in the Crohn’s Disease Intestinal Fibrosis Mouse ModelMediators of Inflammation, 2013
- TNF-α-Secreting B Cells Contribute to Myocardial Fibrosis in Dilated CardiomyopathyJournal of Clinical Immunology, 2013
- Protection against TGF-β1-induced fibrosis effects of IL-10 on dermal fibroblasts and its potential therapeutics for the reduction of skin scarringArchiv für dermatologische Forschung, 2013
- Glycyrrhizin regulates CD4+T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathwayInternational Immunopharmacology, 2012
- Successful Use of mRNA‐Nucleofection for Overexpression of Interleukin‐10 in Murine Monocytes/Macrophages for Anti‐inflammatory Therapy in a Murine Model of Autoimmune MyocarditisJournal of the American Heart Association, 2012
- TGF-β signaling in tissue fibrosis: Redox controls, target genes and therapeutic opportunitiesCellular Signalling, 2012
- Interleukin-10 Treatment Attenuates Pressure Overload–Induced Hypertrophic Remodeling and Improves Heart Function via Signal Transducers and Activators of Transcription 3–Dependent Inhibition of Nuclear Factor-κBCirculation, 2012
- Significance of the Balance between Regulatory T (Treg) and T Helper 17 (Th17) Cells during Hepatitis B Virus Related Liver FibrosisPLOS ONE, 2012