Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis. Mechanistically, the conversion of Treg cells to Tfh cells correlates with reduced expression of IL-2Rα and pSTAT5 levels and increased expression of IL-6Rα. In vitro, incubation of naive T cells with oxLDL prevents their differentiation into Treg cells. Furthermore, injection of lipid-free Apolipoprotein AI (ApoAI) into ApoE^-/- mice reduces intracellular cholesterol levels in Treg cells and prevents their conversion into Tfh cells. Together our results suggest that ApoAI, the main protein in high-density lipoprotein particles, modulates the cellular fate of Treg cells and thus influences the immune response during atherosclerosis.

中文翻译：

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载脂蛋白AI可以防止动脉粥样硬化期间对滤泡辅助性T细胞转换的调节。

调节性T（Treg）细胞有助于动脉粥样硬化形成过程中的抗炎反应。在这里，我们显示在动脉粥样硬化过程中，Treg细胞失去Foxp3表达及其免疫抑制功能，从而导致这些细胞的一部分转化为T卵泡辅助细胞（Tfh）。我们表明，Tfh细胞是促动脉粥样硬化的，其消耗减少了动脉粥样硬化。从机理上讲，Treg细胞向Tfh细胞的转化与IL-2Rα和pSTAT5水平的表达降低以及IL-6Rα的表达升高有关。在体外，将原始T细胞与oxLDL孵育可防止其分化为Treg细胞。此外，将无脂质的载脂蛋白AI（ApoAI）注入ApoE ^-/-小鼠降低Treg细胞中的细胞内胆固醇水平，并阻止其转化为Tfh细胞。我们的研究结果共同表明，高密度脂蛋白颗粒中的主要蛋白ApoAI调节Treg细胞的细胞命运，从而影响动脉粥样硬化期间的免疫反应。