Follicular regulatory helper T cells control the response of regulatory B cells to a high-cholesterol diet

B cell functions in the process of atherogenesis have been investigated but several aspects remain to be clarified.

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.

Our results demonstrate that, through different strategies, both T_FR and T_FH cells modulate anti- and pro-atherosclerotic 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.