Dynamic changes in regulatory T cells are linked to levels of diet-induced hypercholesterolemia.
Dynamic changes in regulatory T cells are linked to levels of diet-induced hypercholesterolemia.
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DOI：
10.1161/circulationaha.110.006411
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发表时间：
2011-07-12
期刊：
影响因子：
37.8
通讯作者：
Lichtman AH
中科院分区：
文献类型：
--
作者：
Maganto-García E;Tarrio ML;Grabie N;Bu DX;Lichtman AH
调节性 T 细胞 (Treg) 存在于动脉粥样硬化病变中，可以调节疾病。在这项研究中，我们描述了与长期高胆固醇血症和病变进展相关的 Treg 反应的变化。 Treg 表达绿色荧光蛋白 (GFP) 的 Ldlr−/− 小鼠被喂食对照或富含胆固醇的饮食，并在淋巴组织和主动脉中计数 GFP+ 细胞。在胆固醇饮食喂养的小鼠中，4周、8周和20周后，脾脏Treg数量增加，然而，循环和病变Treg的数量在4周时达到峰值，并在8周和20周时显着下降，同时伴随着在此期间CD4+效应T细胞数量的增加和病变大小的增加。长期高胆固醇血症后，选择素配体的Treg表达及其与主动脉内皮的结合能力下降，病灶Treg细胞凋亡增加。与喂食胆固醇饮食 8 周的小鼠相比，在喂食 4 周富含胆固醇的饮食后，改用 4 周的对照饮食可降低血清胆固醇，从而阻止病变生长，并且维持高主动脉 Treg 含量。饮食逆转后，脾脏 Treg 保留了 4 周胆固醇饮食后 Treg 的表型。长期的高胆固醇血症会损害病变中的 Treg，但不会损害效应 T 细胞 (Teff)，但逆转高胆固醇血症可以防止病变 Treg 的损失。因此，降低胆固醇疗法可能会引起动脉粥样硬化病变中 Treg:Teff 比率的动态和有益变化。
Regulatory T cells (Treg) are present in atherosclerotic lesions and can modulate disease. In this study we characterized changes in Treg responses associated with prolonged hypercholesterolemia and lesion progression. Ldlr−/− mice in which Treg express green fluorescence protein (GFP) were fed a control or cholesterol-rich diet and GFP+ cells were enumerated in lymphoid tissues and in aorta. Splenic Treg numbers increased after 4, 8 and 20 weeks in cholesterol-diet fed mice, however, the number of circulating and lesional Treg peaked at 4 weeks and decreased significantly at 8 and 20 weeks, concomitant with increased numbers of CD4+ effector T cells and increased lesion size over this period. Treg expression of selectin ligands and their ability to bind to aortic endothelium decreased after prolonged hypercholesterolemia, and apoptosis of lesional Treg increased. After 4 weeks of cholesterol rich-diet, a switch to a control diet for 4 weeks reduced serum cholesterol stopped lesion growth, and the high aortic Treg content was maintained, compared to mice fed a cholesterol diet for 8 weeks. After the diet reversal, the splenic Treg retained the phenotype of Treg after 4 weeks of cholesterol diet. Prolonged hypercholesterolemia impairs Treg but not effector T cell (Teff) accumulation in lesions, but reversal of hypercholesterolemia can prevent loss of lesional Treg. Therefore cholesterol lowering therapies may induce dynamic and beneficial changes in Treg:Teff ratios in atherosclerotic lesions.