miR-142-3p restricts cAMP production in CD4+CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA

被引：229

作者：

Huang, Bo ^{[1
]}

Zhao, Jie ^{[2
]}

Lei, Zhang ^{[1
]}

Shen, Shiqian ^{[3
]}

Li, Dong ^{[1
]}

Shen, Guan-Xin ^{[3
]}

Zhang, Gui-Mei ^{[1
]}

Feng, Zuo-Hua ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430030, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Gynecol & Obstet, Wuhan 430030, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Immunol, Wuhan 430030, Peoples R China

来源：

EMBO REPORTS | 2009年 / 10卷 / 02期

基金：

中国国家自然科学基金;

关键词：

adenylyl cyclase 9; cAMP; FOXP3; miR-142-3p; T cells; GAP-JUNCTION CHANNELS; ANIMAL DEVELOPMENT; MICRORNAS; FOXP3; PERMEABILITY; COMMUNICATION; SUPPRESSION; ACTIVATION; GENES;

D O I：

10.1038/embor.2008.224

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates diverse cellular functions. It has been found that CD4(+)CD25(+) regulatory T (T-REG) cells exert their suppressor function by transferring cAMP to responder T cells. Here, we show that miR-142-3p regulates the production of cAMP by targeting adenylyl cyclase (AC) 9 messenger RNA in CD4(+)CD25(-) T cells and CD4(+)CD25(+) T-REG cells. miR-142-3p limits the level of cAMP in CD4(+)CD25(-) T cells by inhibiting AC9 production, whereas forkhead box P3 (FOXP3) downregulates miR-142-3p to keep the AC9/cAMP pathway active in CD4(+)CD25(-) T-REG cells. These findings reveal a new molecular mechanism through which CD4(+)CD25(+) T-REG cells contain a high level of cAMP for their suppressor function, and also suggest that the microRNA controlling AC expression might restrict the final level of cAMP in various types of cells.

引用

页码：180 / 185

页数：6

共 26 条

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