Regulation of miR-181a expression in T cell aging

被引：65

作者：

Ye, Zhongde ^{[1
,2
]}

Li, Guangjin ^{[1
,2
]}

Kim, Chulwoo ^{[1
,2
]}

Hu, Bin ^{[1
,2
]}

Jadhav, Rohit R. ^{[1
,2
]}

Weyand, Cornelia M. ^{[1
,2
]}

Goronzy, Jorg J. ^{[1
,2
]}

机构：

[1] Stanford Univ, Div Rheumatol & Immunol, Dept Med, Stanford, CA 94305 USA

[2] Vet Affairs Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA 94306 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

美国国家卫生研究院;

关键词：

TRANSCRIPTION FACTOR YY1; YIN YANG 1; INFLUENZA VACCINE; BINDING PROTEIN; DIFFERENTIATION; SENESCENCE; RESPONSES; SELECTION; RECRUITMENT; SENSITIVITY;

D O I：

10.1038/s41467-018-05552-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

MicroRNAs have emerged as key regulators in T cell development, activation, and differentiation, with miR-181a having a prominent function. By targeting several signaling pathways, miR-181a is an important rheostat controlling T cell receptor (TCR) activation thresholds in thymic selection as well as peripheral T cell responses. A decline in miR-181a expression, due to reduced transcription of pri-miR-181a, accounts for T cell activation defects that occur with older age. Here we examine the transcriptional regulation of miR-181a expression and find a putative pri-miR-181a enhancer around position 198,904,300 on chromosome 1, which is regulated by a transcription factor complex including YY1. The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Partial silencing of YY1 in T cells from young individuals reproduces the signaling defects seen in older T cells. In conclusion, YY1 controls TCR signaling by upregulating miR-181a and dampening negative feedback loops mediated by miR-181a targets.

引用

页数：11

共 65 条

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