title: Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function.
abstract: Regulatory T cells (Tregs) play a pivotal role in suppressing immune responses regulating behavior and gene expression in effector T cells, macrophages, and dendritic cells. Tregs infiltrate the infarcted myocardium; however, their role the inflammatory and reparative response after myocardial infarction remains poorly understood. We used FoxP3(EGFP) reporter mice to study Treg trafficking in the infarcted heart and examined the effects of Treg depletion on postinfarction remodeling using an anti-CD25 antibody. Moreover, we investigated the in vitro effects of Tregs on cardiac fibroblast phenotype and function. Low numbers of Tregs infiltrated the infarcted myocardium after 24-72 h of reperfusion. Treg depletion had no significant effects on cardiac dysfunction and scar size after reperfused myocardial infarction but accelerated ventricular dilation and accentuated apical remodeling. Enhanced myocardial dilation in Treg-depleted animals was associated with increased expression of chemokine (C-C motif) ligand 2 and accentuated macrophage infiltration. In vitro, Tregs modulated the cardiac fibroblast phenotype, reducing expression of α-smooth muscle actin, decreasing expression of matrix metalloproteinase-3, and attenuating contraction of fibroblast-populated collagen pads. Our findings suggest that endogenous Tregs have modest effects on the inflammatory and reparative response after myocardial infarction. However, the anti-inflammatory and matrix-preserving properties of Tregs may suggest a role for Treg-based cell therapy in the attenuation of adverse postinfarction remodeling.
authors.affiliation: The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York; and.
authors.forename: Amit
authors.initials: A
authors.lastname: Saxena
authors.affiliation: The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York; and.
authors.forename: Marcin
authors.initials: M
authors.lastname: Dobaczewski
authors.affiliation: The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York; and.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Rai
authors.affiliation: The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York; and.
authors.forename: Zaffar
authors.initials: Z
authors.lastname: Haque
authors.affiliation: The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York; and.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York; and Department of Medicine, Baylor College of Medicine, Houston, Texas nikolaos.frangogiannis@einstein.yu.edu.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Frangogiannis
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000502:physiology; D020257:Ventricular Remodeling
chemical_list: D000199:Actins; D054405:Chemokine CCL3; C544013:alpha-smooth muscle actin, mouse; D003094:Collagen; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse
keywords: fibroblast; inflammation; lymphocyte; myocardial infarction; remodeling