Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.
Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.
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调节性 T 细胞的强粘附诱导树突状细胞细胞骨架极化和接触依赖性嗜睡
DOI：
10.1084/jem.20160620
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Shi Y
中科院分区：
文献类型：
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作者：
Chen J;Ganguly A;Mucsi AD;Meng J;Yan J;Detampel P;Munro F;Zhang Z;Wu M;Hari A;Stenner MD;Zheng W;Kubes P;Xia T;Amrein MW;Qi H;Shi Y
树突状细胞被调节性T（T reg）细胞靶向，以作为T细胞抑制的间接模式起作用。在这项研究中，使用单细胞力谱和结构化照明显微镜相结合，我们分析了单个T reg细胞-DC相互作用的事件，并显示T reg细胞表现出强大的内在免疫力。这种增加的DC粘附降低了接触的DC接合其他抗原特异性细胞的能力。我们发现，这种异常强烈的LFA-1依赖性的T reg细胞粘附部分是由它们的低钙蛋白酶活性引起的，钙蛋白酶活性通常会释放整合素-细胞骨架连接，从而减少粘附。超分辨率成像显示，这种T reg细胞粘附导致Fascin-1（一种免疫突触形成所必需的肌动蛋白捆绑蛋白）的隔离，并使DC中Fascin-1依赖的肌动蛋白极化向T reg细胞粘附区倾斜。虽然它在T reg细胞脱离后是可逆的，但这种基本细胞骨架组分的隔离导致DC的昏睡状态，导致T细胞引发减少。我们的研究结果揭示了一个动态的细胞骨架成分的基础T细胞介导的DC抑制在接触依赖性的方式。
Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell–DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1–dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin–cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1–dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell–mediated DC suppression in a contact-dependent manner.