Cellular and Molecular Biology Department, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain; and.
Medical Research Council-Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
J Immunol. 2019 Mar 15;202(6):1715-1723. doi: 10.4049/jimmunol.1800575. Epub 2019 Feb 4.
The immunological synapse (IS) is a superstructure formed during T cell activation at the zone of contact between T cells and dendritic cells (DCs). The IS includes specific molecular components in the T cell and DCs sides that may result in different functionality. Most of the studies on the IS have focused on the T cell side of this structure and, in contrast, the information available on the IS of DCs is sparse. Autophagy is a cellular process involved in the clearance of damaged proteins and organelles via lysosomal degradation. Mitophagy is the selective autophagy of damaged mitochondria. In this study, it is shown that IS formation induces clustering of mitochondria in the IS of DCs and partial depolarization of these organelles. At the IS of the DCs also accumulate autophagy and mitophagy markers, even when the kinase complex mTORC1, an inhibitor of the autophagy, is active. Together the results presented indicate that IS formation induces local clustering of mitochondria and mitophagy, which could be a homeostatic mechanism to control the quality of mitochondria in this region. The data underline the complexity of the regulatory mechanisms operating in the IS of DCs.
免疫突触(IS)是 T 细胞与树突状细胞(DC)接触区在 T 细胞激活过程中形成的超结构。IS 包括 T 细胞和 DC 侧的特定分子成分,这些成分可能导致不同的功能。大多数关于 IS 的研究都集中在这个结构的 T 细胞侧,相比之下,关于 DC 的 IS 的信息则很匮乏。自噬是一种细胞过程,通过溶酶体降解来清除受损的蛋白质和细胞器。线粒体自噬是受损线粒体的选择性自噬。在这项研究中,研究表明 IS 的形成诱导了 DC 中 IS 中线粒体的聚集和这些细胞器的部分去极化。在 DC 的 IS 中也积累了自噬和线粒体自噬的标志物,即使激酶复合物 mTORC1(自噬的抑制剂)是活跃的。总之,所呈现的结果表明,IS 的形成诱导了线粒体的局部聚集和线粒体自噬,这可能是一种在该区域控制线粒体质量的动态平衡机制。这些数据强调了在 DC 的 IS 中起作用的调控机制的复杂性。