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, Treg cell 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 Treg cells (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 Treg cells (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 Treg cell defects in CHD patients. Our findings emphasize the important role of the CD31+ Tr subpopulation in maintaining Treg cell normal function and may provide a novel explanation for impaired immunoregulation of Treg cells in CHD.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have