TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7
TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7
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DOI：
10.1038/gene.2012.45
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发表时间：
2012-12-01
影响因子：
5
通讯作者：
Yang, R.
中科院分区：
文献类型：
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作者：
Min, S.;Li, L.;Yang, R.
树突状细胞(DC)在肿瘤微环境中诱导的变化尚未被广泛研究。我们发现，肿瘤相关因子转化生长因子-β可能通过SP1转录因子选择性上调miR-27A的表达。重要的是，miR-27A改变了NF-kappa B和MAPKs(丝裂原活化蛋白激酶)p38、JNK(c-jun氨基末端激酶)和ERK(细胞外信号调节激酶1/2)的活性。它通过靶向Tab3、p38MAPK、MAP2K4和MAP2K7影响促炎细胞因子的产生。因此，miR-27A在体内外抑制了DC介导的Th1和Th17细胞的分化，但促进了DC介导的TR1(CD4(+)IL-10(+))和Treg(CD4(+)CD25(+)Foxp3(+))细胞在体内的聚集。将miR-27A基因工程的DC反复注入肿瘤组织，加速了肿瘤的生长，表明miR-27A是肿瘤免疫治疗的潜在靶点。《基因与免疫》(2012年)13621-631；DOI：10.1038/gene.2012.45；2012年10月4日在线发布
The alterations induced in dendritic cells (DCs) in the cancer microenvironment have not been extensively explored. We found that the tumor-associated factor TGF-beta may selectively upregulate the expression of miR-27a via the SP1 transcription factor. Importantly, miR-27a altered the activity of NF-kappa B 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. Genes and Immunity (2012) 13, 621-631; doi:10.1038/gene.2012.45; published online 4 October 2012