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TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7.
- Source :
- Genes & Immunity; Dec2012, Vol. 13 Issue 8, p621-631, 11p
- Publication Year :
- 2012
-
Abstract
- The alterations induced in dendritic cells (DCs) in the cancer microenvironment have not been extensively explored. We found that the tumor-associated factor TGF-β may selectively upregulate the expression of miR-27a via the SP1 transcription factor. Importantly, miR-27a altered the activity of NF-κB and MAPKs (mitogen-activated protein kinases) p38, JNK (c-Jun N-terminal kinases) and ERK (extracellular signal-regulated kinase 1/2). It influences the production of proinflammatory cytokines by targeting TAB3, p38 MAPK, MAP2K4 and MAP2K7. As a consequence, miR-27a hampered the DC-mediated differentiation of Th1 and Th17 cells in vitro and in vivo, but it promoted the DC-mediated accumulation of Tr1 (CD4<superscript>+</superscript>IL-10<superscript>+</superscript>) and Treg (CD4<superscript>+</superscript>CD25<superscript>+</superscript>Foxp3<superscript>+</superscript>) cells in vivo. The repeated infusion of miR-27a-engineered DCs into tumor tissues accelerated tumor growth, indicating that miR-27a is a potential target for tumor immunotherapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14664879
- Volume :
- 13
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Genes & Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 83928376
- Full Text :
- https://doi.org/10.1038/gene.2012.45