Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile.
J Immunol. 2011 Sep 15;187(6):3121-32. doi: 10.4049/jimmunol.1100378. Epub 2011 Aug 15.
Gap junction (GJ) mediates intercellular communication through linked hemichannels from each of two adjacent cells. Using human and mouse models, we show that connexin 43 (Cx43), the main GJ protein in the immune system, was recruited to the immunological synapse during T cell priming as both GJs and stand-alone hemichannels. Cx43 accumulation at the synapse was Ag specific and time dependent, and required an intact actin cytoskeleton. Fluorescence recovery after photobleaching and Cx43-specific inhibitors were used to prove that intercellular communication between T cells and dendritic cells is bidirectional and specifically mediated by Cx43. Moreover, this intercellular cross talk contributed to T cell activation as silencing of Cx43 with an antisense or inhibition of GJ docking impaired intracellular Ca(2+) responses and cytokine release by T cells. These findings identify Cx43 as an important functional component of the immunological synapse and reveal a crucial role for GJs and hemichannels as coordinators of the dendritic cell-T cell signaling machinery that regulates T cell activation.
间隙连接 (GJ) 通过来自两个相邻细胞的每个连接的半通道介导细胞间通讯。使用人类和小鼠模型，我们表明，间隙连接蛋白 43 (Cx43)，免疫系统中的主要 GJ 蛋白，在 T 细胞启动过程中被募集到免疫突触，既是 GJ 也是独立的半通道。Cx43 在突触处的积累是 Ag 特异性和时间依赖性的，需要完整的肌动蛋白细胞骨架。荧光恢复后光漂白和 Cx43 特异性抑制剂的使用证明了 T 细胞和树突状细胞之间的细胞间通讯是双向的，并且由 Cx43 特异性介导。此外，这种细胞间的串扰有助于 T 细胞的激活，因为用反义寡核苷酸沉默 Cx43 或抑制 GJ 对接会损害 T 细胞的细胞内 Ca(2+)反应和细胞因子释放。这些发现确定 Cx43 是免疫突触的重要功能组成部分，并揭示了 GJ 和半通道作为协调树突状细胞-T 细胞信号机制的关键作用，该机制调节 T 细胞的激活。
