title: miR-142-3p restricts cAMP production in CD4+CD25- T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA.
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.
authors.affiliation: 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
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lei
authors.forename: Shiqian
authors.initials: S
authors.lastname: Shen
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Guan-Xin
authors.initials: GX
authors.lastname: Shen
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Zhang
authors.forename: Zuo-Hua
authors.initials: ZH
authors.lastname: Feng
mesh_terms: 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
chemical_list: 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