miR-142-3p restricts cAMP production in CD4+CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA.
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.
Huang
Bo
B
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
J
Lei
Zhang
Z
Shen
Shiqian
S
Li
Dong
D
Shen
Guan-Xin
GX
Zhang
Gui-Mei
GM
Feng
Zuo-Hua
ZH
D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014162:Transfection
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D012333:RNA, Messenger; D000242:Cyclic AMP; D000262:Adenylyl Cyclases