期刊
EMBO REPORTS
卷 10, 期 2, 页码 180-185出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2008.224
关键词
adenylyl cyclase 9; cAMP; FOXP3; miR-142-3p; T cells
资金
- National Development Program (973) For Key Basic Research of China [2002CB513100]
- National Natural Science Foundation of China [30771974, 30471587]
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.
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