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

B Huang, J Zhao, Z Lei, S Shen, D Li, GX Shen… - EMBO …, 2009 - embopress.org
B Huang, J Zhao, Z Lei, S Shen, D Li, GX Shen, GM Zhang, ZH Feng
EMBO reports, 2009embopress.org
Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates diverse cellular
functions. It has been found that CD4+ CD25+ regulatory T (TREG) 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+ TREG cells. miR‐142‐3p limits the level of cAMP
in CD4+ CD25− T cells by inhibiting AC9 production, whereas forkhead box P3 (FOXP3) …
Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates diverse cellular functions. It has been found that CD4+CD25+ regulatory T (TREG) 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+ TREG 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+ TREG cells. These findings reveal a new molecular mechanism through which CD4+CD25+ TREG 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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