TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7.

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(+)IL-10(+)) and Treg (CD4(+)CD25(+)Foxp3(+)) 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.

• Authors: S Min, L Li, M Zhang, Y Zhang, X Liang, Y Xie, Q He, Y Li, J Sun, Q Liu, X Jiang, Y Zhang, Y Che, R Yang
• Journal: Genes and immunity (Genes Immun) Vol. 13 Issue 8 Pg. 621-31 (Dec 2012) ISSN: 1476-5470 [Electronic] England
• PMID: 23034448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Intracellular Signaling Peptides and Proteins
• MIRN27 microRNA, human
• MicroRNAs
• TAB3 protein, human
• Transforming Growth Factor beta
• Mitogen-Activated Protein Kinases

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Base Sequence
• Cell Communication
• Cell Differentiation
• Cell Line, Tumor
• Dendritic Cells (drug effects, metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• MAP Kinase Signaling System
• Macrophages (drug effects, metabolism, pathology)
• Mice
• MicroRNAs (genetics, metabolism)
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• Molecular Sequence Data
• Monocytes (drug effects, metabolism, pathology)
• Oligonucleotide Array Sequence Analysis
• Signal Transduction
• Th1 Cells (drug effects, metabolism, pathology)
• Th17 Cells (drug effects, metabolism, pathology)
• Transforming Growth Factor beta (metabolism, pharmacology)