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PMID: 19098714 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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

EMBO reports ·Vol. 10 ·No. 2 ·2009-02-00 ·Pages 180-5

Huang B, Zhao J, Lei Z, Shen S, Li D, Shen GX, Zhang GM, Feng ZH

Abstract

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.

MeSH Terms
Adenylyl Cyclases/biosynthesis,genetics Animals CD4 Antigens/analysis CD4-Positive T-Lymphocytes/metabolism Cyclic AMP/biosynthesis Enzyme Induction/genetics Forkhead Transcription Factors/physiology Interleukin-2 Receptor alpha Subunit/analysis Mice Mice, Inbred BALB C MicroRNAs/genetics,physiology RNA, Messenger/antagonists & inhibitors,genetics T-Lymphocyte Subsets/metabolism T-Lymphocytes, Regulatory/metabolism Transfection
Chemicals
CD4 Antigens Forkhead Transcription Factors Foxp3 protein, mouse Interleukin-2 Receptor alpha Subunit MicroRNAs Mirn142 microRNA, mouse RNA, Messenger Cyclic AMP Adenylyl Cyclases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Huang Bo
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China. tjhuangbo@hotmail.com
Zhao Jie
Lei Zhang
Shen Shiqian
Li Dong
Shen Guan-Xin
Zhang Gui-Mei
Feng Zuo-Hua
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-3178
DOI
10.1038/embor.2008.224
Email
tjhuangbo@hotmail.com
Published
2009-02-00
Epub
2008-00-19
Pages
180-5
Language
English
Region
England
NLM ID
100963049
PMCID
PMC2637310
Subset
IM
External Links
PubMed source DOI: 10.1038/embor.2008.224 PMC Full Text View journal details
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