Age-dependent changes in the sphingolipid composition of mouse CD4+ T cell membranes and immune synapses implicate glucosylceramides in age-related T cell dysfunction.
Age-dependent changes in the sphingolipid composition of mouse CD4+ T cell membranes and immune synapses implicate glucosylceramides in age-related T cell dysfunction.
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DOI：
10.1371/journal.pone.0047650
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Meydani SN
中科院分区：
文献类型：
--
作者：
Molano A;Huang Z;Marko MG;Azzi A;Wu D;Wang E;Kelly SL;Merrill AH Jr;Bunnell SC;Meydani SN
为了确定鞘脂成分的变化是否与年龄相关的免疫功能障碍有关，我们分析了年轻和老年 CD4+ T 细胞的核心鞘脂组（即通过第一个头基添加的所有代谢物）。由于鞘脂影响膜的生物物理特性，我们评估了免疫突触 (IS) 和通过磁免疫分离制备的非 IS 部分的组成。总体而言，在老化的 CD4+ T 细胞中发现鞘磷脂、二氢鞘磷脂和神经酰胺的含量增加。总鞘脂含量标准化后，老化 T 细胞的非 IS 和 IS 部分中葡萄糖神经酰胺的摩尔分数均出现统计学上显着的下降。这种变化通过老化 CD4+ T 细胞中鞘磷脂和二氢鞘磷脂摩尔分数的不太显着增加来平衡。在体外，神经酰胺水平的直接或酶促增强降低了 CD4+ T 细胞的增殖，而不考虑响应 T 细胞的年龄。相比之下，体外抑制葡萄糖神经酰胺酶优先增加老化 CD4+ T 细胞的增殖。这些结果表明，葡萄糖神经酰胺丰度的减少会导致 CD4+ T 细胞功能与年龄相关的损伤。
To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4+ T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions of immune synapse (IS) and non-IS fractions prepared by magnetic immuno-isolation. Broadly, increased amounts of sphingomyelins, dihydrosphingomyelins and ceramides were found in aged CD4+ T cells. After normalizing for total sphingolipid content, a statistically significant decrease in the molar fraction of glucosylceramides was evident in both the non-IS and IS fractions of aged T cells. This change was balanced by less dramatic increases in the molar fractions of sphingomyelins and dihydrosphingomyelins in aged CD4+ T cells. In vitro, the direct or enzymatic enhancement of ceramide levels decreased CD4+ T cell proliferation without regard for the age of the responding T cells. In contrast, the in vitro inhibition of glucosylceramidase preferentially increased the proliferation of aged CD4+ T cells. These results suggest that reductions in glucosylceramide abundance contribute to age-related impairments in CD4+ T cell function.
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影响因子：
4.4
作者：
Marko, Melissa G.;Ahmed, Tanvir;Meydani, Simin Nikbin
通讯作者：
Meydani, Simin Nikbin
影响因子：
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作者：
Blank, N;Schiller, M;Lorenz, HM
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作者：
Barbat, Christiane;Trucy, Maylis;Mazerolles, Fabienne
通讯作者：
Mazerolles, Fabienne
影响因子：
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Merrill, AH;Sullards, MC;Wang, E
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Wang, E
影响因子：
15.9
作者：
MARSH, NL;ELIAS, PM;HOLLERAN, WM
通讯作者：
HOLLERAN, WM