Interleukin-10 reorganizes the cytoskeleton of mature dendritic cells leading to their impaired biophysical properties and motilities.
Interleukin-10 reorganizes the cytoskeleton of mature dendritic cells leading to their impaired biophysical properties and motilities.
复制标题
Interleukin-10 重组成熟树突状细胞的细胞骨架，导致其生物物理特性和运动能力受损
DOI：
10.1371/journal.pone.0172523
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zeng Z
中科院分区：
文献类型：
--
作者：
Xu X;Liu X;Long J;Hu Z;Zheng Q;Zhang C;Li L;Wang Y;Jia Y;Qiu W;Zhou J;Yao W;Zeng Z
白细胞介素-10 （IL-10）是一种主要诱导免疫耐受的免疫调节细胞因子。它也被确定为肿瘤微环境中的主要细胞因子，显著介导肿瘤免疫逃逸。以往关于IL-10在肿瘤免疫抑制中的作用的研究主要集中在其生化作用上。但IL-10对免疫细胞生物物理特性的影响尚不明确。树突状细胞（dc）是最有效的抗原呈递细胞，在抗肿瘤免疫应答中起关键作用。IL-10可通过多种途径影响dc的免疫调节功能。在本研究中，我们旨在探讨IL-10对成熟dc （mDCs）生物物理功能的影响。用不同浓度的IL-10处理mDCs，并鉴定其生物物理特性。结果表明，IL-10影响了mDCs的生物物理性能，包括电泳迁移率、渗透脆弱性和变形性，以及它们的运动性。同时，细胞骨架（F-actin）被IL-10重组。IL-10引起fasin1和profin1的表达变化以及cofilin1的磷酸化呈浓度依赖性。傅里叶变换红外共振数据显示，IL-10使mDCs的基因转录和代谢转换状态更加活跃。这些结果揭示了IL-10对免疫系统作用的一个新方面，并代表了肿瘤免疫逃逸的机制之一。这可能为优化和提高基于dc的肿瘤免疫治疗效率提供有价值的线索。
Interlukin-10 (IL-10) is an immunomodulatory cytokine which predominantly induces immune-tolerance. It has been also identified as a major cytokine in the tumor microenvironment that markedly mediates tumor immune escape. Previous studies on the roles of IL-10 in tumor immunosuppression mainly focus on its biochemical effects. But the effects of IL-10 on the biophysical characteristics of immune cells are ill-defined. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a key role in the anti-tumor immune response. IL-10 can affect the immune regulatory functions of DCs in various ways. In this study, we aim to explore the effects of IL-10 on the biophysical functions of mature DCs (mDCs). mDCs were treated with different concentrations of IL-10 and their biophysical characteristics were identified. The results showed that the biophysical properties of mDCs, including electrophoresis mobility, osmotic fragility and deformability, as well as their motilities, were impaired by IL-10. Meanwhile, the cytoskeleton (F-actin) of mDCs was reorganized by IL-10. IL-10 caused the alternations in the expressions of fasin1 and profilin1 as well as the phosphorylation of cofilin1 in a concentration-dependent fashion. Moreover, Fourier transformed infrared resonance data showed that IL-10 made the status of gene transcription and metabolic turnover of mDCs more active. These results demonstrate a new aspect of IL-10’s actions on the immune system and represent one of the mechanisms for immune escape of tumors. It may provide a valuable clue to optimize and improve the efficiency of DC-based immunotherapy against cancer.