Science:衰老造成CD4+T细胞免疫力下降和基因表达不稳定

2017-03-31 leo.c MedSci原创

年轻的CD4+T细胞在受到刺激后,就算来自不同种族的CD4+T细胞,也统一的表达调节免疫的关键基因群。相反,年老的CD4+T细胞在受到刺激后,节免疫的关键基因群的表达程度下降,但是细胞和细胞间的基因表达的一致性下降,造成了更多的个体差异。这项研究,为衰老引起的免疫力低下,以及基因表达的不稳定和突变几率的上升提供了理论支持。

衰老常常伴随着逐步的失去原有的身体机能以及细胞功能,但是在这之后的分子机制并没有被了解的很清楚。机体免疫系统中的CD4+和CD8+T细胞,就是典型的衰老影响细胞功能的例子。随着衰老, CD4+和CD8+T细胞原有的对抗感染及杀死异常增殖细胞(癌细胞)的能力就有所下降,从而导致感染及癌症发生率的上升。

在最新的一期Science杂志中,来自英国剑桥大学的Celia Pilar Martinez-Jimenez及其同事报道了他们的发现:CD4+细胞的衰老能够影响细胞的基因表达,降低免疫基因的表达,反而随机无序的上调其他基因的表达,从而降低了CD4+细胞的免疫能力。

研究人员首先比对了从两种不同实验鼠(Mus musculus domesticus (B6), and Mus musculus castaneus (CAST))分离的CD4+T细胞的基因表达特征,发现在不受任何刺激的情况下,这两种老鼠的CD4+T细胞的基因表达特征有所不同。然而当用特定的蛋白(CD3CD28 ligand)刺激年轻的(3个月内)CD4+T细胞后,这些本来因为种别造成的基因表达的不同,相对于激活后造成的不同显得微不足道。相反,在激活后的T细胞内,两种老鼠的CD4+T细胞的基因表达特征及其参与的反应作用都有很高的相似性。在激活后的T细胞内,大约有36%的基因上调,大约有18%的基因下调。因此根据这些在刺激后区别表达的基因,研究组将其归纳为调节免疫的关键基因群。

相对的,但研究组对衰老的(21个月后)CD4+T细胞进行同样的刺激后,发现这些调节免疫的关键基因群的表达量总体下降。有趣的是,其他的一些基因的表达量上升。通过对上调的基因进行信号通路及功能的分析,发现这些上调的基因随机分布于不同功能,并没有特定的信号通路的基因有统一的高表达。并且,不同细胞间的高表达基因根据细胞也有所不同,没有一致性。

因此研究者归纳,年轻的CD4+T细胞在受到刺激后,就算来自不同种族的CD4+T细胞,也统一的表达调节免疫的关键基因群。相反,年老的CD4+T细胞在受到刺激后,节免疫的关键基因群的表达程度下降,但是细胞和细胞间的基因表达的一致性下降,造成了更多的个体差异。这项研究,为衰老引起的免疫力低下,以及基因表达的不稳定和突变几率的上升提供了理论支持。

原始出处:

Celia Pilar Martinez-Jimenez, Nils Eling, Hung-Chang Chen, Aging increases cell-to-cell transcriptional variability upon immune stimulation. Science  31 Mar 2017:Vol. 355, Issue 6332, pp. 1433-1436DOI: 10.1126/science.aah4115

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    2017-12-01 xuyu
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    2017-08-09 qidongfanjian
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    2017-04-11 春暖花开8785

    衰老研究已经达到分子水平了。

    0

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    2017-04-03 虈亣靌

    全程参与实验,即学即用,多次实践,确保掌握所学技术。

    0

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    2017-04-02 jichang
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