Department of Immunology, Nankai University School of Medicine, Tianjin, China; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
Department of Immunology, Nankai University School of Medicine, Tianjin, China.
PLoS One. 2015 Mar 31;10(3):e0121510. doi: 10.1371/journal.pone.0121510. eCollection 2015.
Dendritic cells (DCs) play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22) as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR) of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.
树突状细胞 (DCs) 在触发抗肿瘤免疫反应中发挥着关键作用。其细胞内 p38 信号在控制 DC 活性方面非常重要。在这项研究中，我们发现 microRNA-22 (miR-22) 通过直接结合其 mRNA 的 3'非翻译区 (3'UTR) 抑制 p38 蛋白的表达。p38 的下调进一步干扰了 DC 衍生的 IL-6 的合成和 DC 驱动的 Th17 细胞的分化。此外，在 DC 中过表达 miR-22 会损害其抑制肿瘤的能力，而 miR-22 抑制剂可以逆转这种现象并提高基于 DC 的免疫疗法的疗效。因此，我们的研究结果强调了 miR-22 在 DC 诱导的抗肿瘤免疫过程中的抑制作用，阻断这种 miRNA 为癌症患者生成有效的 DC 疫苗提供了一种新策略。
