Biomechanical alterations of dendritic cells by co-culturing with K562 CML cells and their potential role in immune escape.
Biomechanical alterations of dendritic cells by co-culturing with K562 CML cells and their potential role in immune escape.
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DOI：
10.1016/j.jbiomech.2010.04.028
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发表时间：
2010-08
影响因子：
2.4
通讯作者：
Xiaofeng Xu;Z. Zeng;W. Yao;Xianwei Wang;Dagong Sun;W. Ka;Yingyu Zhang;Xifu Wang;Xiaopeng Chen;Yi Zha;Li Sun;Lide Xie;Z. Wen;S. Chien
中科院分区：
文献类型：
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作者：
Xiaofeng Xu;Z. Zeng;W. Yao;Xianwei Wang;Dagong Sun;W. Ka;Yingyu Zhang;Xifu Wang;Xiaopeng Chen;Yi Zha;Li Sun;Lide Xie;Z. Wen;S. Chien
树突状细胞(DC)是一种强大的抗原提呈细胞(APC)，它被用来传递启动免疫反应所必需的信号。在这项研究中，我们使用跨学科的方法来表征人类慢性粒细胞白血病(CML)细胞系K562细胞对DC生物力学特性和免疫功能的影响。未成熟树突状细胞(ImDC)和成熟树突状细胞(MDCs)与K562细胞共培养时，其生物力学和免疫学特性均较对照组严重受损。这些变化包括膜粘弹性增加，重组细胞骨架(F-肌动蛋白)，抗原摄取能力受到抑制，跨内皮细胞迁移，以及幼稚T细胞的激活。为了探讨这些变化的机制，我们通过芯片分析和双向凝胶电泳法鉴定了几个基因和蛋白质。细胞骨架相关基因和蛋白(如cofilin1和profilin1)和基质相关基因和蛋白(如TIMP1和MMP9)发生了变化。这些发现为研究K562对DC的生物力学和免疫学变化提供了分子基础，并可能有助于阐明肿瘤免疫逃逸的机制。
Dendritic cells (DCs), which are potent antigen presenting cells (APCs), are utilized to deliver the signals essential for the initiation of immune responses. In this study, we used an interdisciplinary approach to characterize the effect of K562 cells, a human chronic myeloid leukemia (CML) cell line, on the biomechanical characteristics and immune functions of DCs. When co-cultured with K562 cells, the biomechanical and immunological characteristics of immature DCs (imDCs) and mature DCs (mDCs) were severely impaired compared with controls. The changes include increased membrane viscoelasticity, reorganized cytoskeleton (F-actin), suppressed capability of antigen uptake, transendothelium migration, and activation of naïve T cells. In exploring the mechanisms of these changes, we identified several genes and proteins by microarray analysis and 2D gel electrophoresis. Changes were found in the cytoskeleton-related genes and proteins (such as cofilin1 and profilin1) and matrix-related genes and proteins (such as TIMP1 and MMP9). These findings provide a molecular basis for the biomechanical and immunological changes of DCs in response to K562 and may help to elucidate the mechanism for tumor immune escape.