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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

Genes & Immunity volume 13, pages 621–631 (2012)Cite this article

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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.

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Acknowledgements

This research was supported by NSFC grants 91029736, 30771967 and 30872315, the Ministry of Science and Technology grants (863 program, 2008AA02Z129), the National Theme Program of China (863 Program, 2011AA020116), and the National Key Scientific Program (2011CB964902).

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Authors and Affiliations

  1. Department of Immunology, Nankai University School of Medicine, Tianjin, China

    S Min, L Li, M Zhang, Y Zhang, X Liang, Y Xie, Q He, Q Liu, X Jiang, Y Zhang, Y Che & R Yang

  2. Tianjin ‘254’ Hospital, Nankai University, Tianjin, China

    Y Li & J Sun

  3. Key Laboratory of Bioactive Materials, Ministry of Education, Tianjin, China

    R Yang

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Min, S., Li, L., Zhang, M. et al. TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7. Genes Immun 13, 621–631 (2012). https://doi.org/10.1038/gene.2012.45

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