title: Decreased frequencies and impaired functions of the CD31+subpopulation in Tregcells associated with decreased FoxP3 expression and enhanced Tregcell defects in patients with coronary heart disease.
abstract: Coronary heart disease (CHD) is one of the most common types of organ lesions caused by atherosclerosis, in which CD4+CD25+forkhead box protein 3 (FoxP3+) regulatory T cells (Treg) play an atheroprotective role. However, Tregcell numbers are decreased and their functions are impaired in atherosclerosis; the underlying mechanisms remain unclear. CD31 plays an important part in T cell response and contributes to maintaining T cell tolerance. The immunomodulatory effects of CD31 are also implicated in atherosclerosis. In this study, we found that decreased frequencies of the CD31+subpopulation in Tregcells (CD31+Tr cells) correlated positively with decreased FoxP3 expression in CHD patients. Cell culture in vitro demonstrated CD31+Tr cells maintaining stable FoxP3 expression after activation and exhibited enhanced proliferation and immunosuppression compared with the CD31-subpopulation in Tregcells (CD31-Tr cells). We also confirmed impaired secretion of transforming growth factor (TGF)-β1 and interleukin (IL)-10 in CD31+Tr cells of CHD patients. Further analysis revealed reduced phospho-SHP2 (associated with CD31 activation) and phospho-signal transducer and activator of transcription-5 (STAT-5) (associated with FoxP3 transcription) levels in CD31+Tr cells of CHD patients, suggesting that decreased FoxP3 expression in CD31+Tr cells might be because of attenuated SHP2 and STAT-5 activation. These data indicate that decreased frequencies and impaired functions of the CD31+Tr subpopulation associated with decreased FoxP3 expression give rise, at least in part, to Tregcell defects in CHD patients. Our findings emphasize the important role of the CD31+Tr subpopulation in maintaining Tregcell normal function and may provide a novel explanation for impaired immunoregulation of Tregcells in CHD.
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Shen
mesh_terms: D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D050799:STAT5 Transcription Factor; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: CD31; FoxP3; Treg cell; atherosclerosis; coronary heart disease