Abstract
Atherosclerosis is a chronic inflammatory disease involving the infiltration of immune cells, such as monocytes/macrophages, neutrophils, T cells, and B cells, into the inner layer of vessel walls. T and B cell functions in the process of atherogenesis, as well as their mutual regulation, have been investigated but several aspects remain to be clarified. In the present review, we give a brief overview of the functions of follicular regulatory T cell (Tfr) on follicular T (Tfh) and B cell regulation related to atherosclerosis pathogenesis, including their influence on lymphangiogenesis and lipoprotein metabolism. We will also discuss their potential therapeutics properties in the resolution of established atherosclerotic lesions.
Highlights
Cardiovascular diseases (CVD) are the leading cause of mortality worldwide.[1]
We give a brief overview of the functions of follicular regulatory T cell (Tfr) on follicular T (Tfh) and B cell regulation related to atherosclerosis pathogenesis, including their influence on lymphangiogenesis and lipoprotein metabolism
We will try to give an overview of the functions of immune cells in the regulation of atherosclerosis with particular emphasis on regulatory B cells (Breg), follicular T cell (Tfh), and follicular regulatory T cell (Tfr)
Summary
Cardiovascular diseases (CVD) are the leading cause of mortality worldwide.[1]. Atherosclerosis is the most studied CVD. Treg cells have proven to have a direct effect on endothelial cell activation, lymphocyte infiltration, foam cell formation, and on macrophage differentiation.[47,57] During atherosclerosis, Treg cells can lose FoxP3 and mutate into memory, IFN-γ+ or Tfh cells.[26,58] During this process, cells lose their ability to produce TGF-β1, a cytokine known to be atheroprotective and for its ability to modulate Tfh cell population.[59,60] Lymphangiogenesis is inhibited through Tfh-dependent IL-4 secretion.[61,62] Diminishing Tfh cells and, in turn, IL-4 expression in mice increases the lymphangiogenesis.[25,27] Due to their close phenotypical characteristics, there is no study in our knowledge in which Tfh cell population is investigated independently of Tfr cells. Our data demonstrate that Tfr population stimulates directly lymphangiogenesis and Breg cells proliferation.[27,68] They suggest that Tfr cell population seems to have more significant functions in
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