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Aims B cell functions in the process of atherogenesis have been investigated but several aspects remain to be clarified. Methods and results In this study, we show that follicular regulatory helper T cells (T-FR) control regulatory B cell (B-REG) populations in Apoe(-/)(-) mice models on a high-cholesterol diet (HCD). Feeding mice with HCD resulted in up-regulation of T-FR and B-REG cell populations, causing the suppression of proatherogenic follicular helper T cell (T-FH) response. T-FH cell modulation is correlated with the growth of atherosclerotic plaque size in thoracoabdominal aortas and aortic root plaques, suggesting that T-FR cells are atheroprotective. During adoptive transfer experiments, T-FR cells transferred into HCD mice decreased T-FH cell populations, atherosclerotic plaque size, while B-REG cell population and lymphangiogenesis are significantly increased. Conclusion Our results demonstrate that, through different strategies, both T-FR and T-FH cells modulate anti- and proatherosclerotic immune processes in an Apoe(-/-) mice model since T-FR cells are able to regulate both T-FH and B-REG cell populations as well as lymphangiogenesis and lipoprotein metabolism. [GRAPHICS] .