Immunology Service, Instituto de Investigación Sanitaria del Hospital Universitario La Princesa (IIS-Princesa), Madrid, Spain.
Immunology, Oftalmology and Otorrinolaryngology Dept., School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain.
Front Immunol. 2023 Jul 13;14:1197289. doi: 10.3389/fimmu.2023.1197289. eCollection 2023.
The organization of the mitochondrial network is relevant for the metabolic fate of T cells and their ability to respond to TCR stimulation. This arrangement depends on cytoskeleton dynamics in response to TCR and CD28 activation, which allows the polarization of the mitochondria through their change in shape, and their movement along the microtubules towards the immune synapse. This work focus on the role of End-binding protein 1 (EB1), a protein that regulates tubulin polymerization and has been previously identified as a regulator of intracellular transport of CD3-enriched vesicles. EB1-interferred cells showed defective intracellular organization and metabolic strength in activated T cells, pointing to a relevant connection of the cytoskeleton and metabolism in response to TCR stimulation, which leads to increased AICD. By unifying the organization of the tubulin cytoskeleton and mitochondria during CD4 T cell activation, this work highlights the importance of this connection for critical cell asymmetry together with metabolic functions such as glycolysis, mitochondria respiration, and cell viability.
线粒体网络的组织对于 T 细胞的代谢命运及其对 TCR 刺激做出反应的能力至关重要。这种排列取决于细胞骨架对 TCR 和 CD28 激活的动态反应，这允许通过改变线粒体的形状和沿着微管向免疫突触移动来实现线粒体的极化。这项工作集中在末端结合蛋白 1（EB1）的作用上，EB1 是一种调节微管聚合的蛋白质，先前被确定为富含 CD3 的囊泡细胞内运输的调节剂。EB1 干扰细胞显示出激活的 T 细胞中细胞内组织和代谢强度的缺陷，这表明细胞骨架和代谢对 TCR 刺激的反应之间存在着重要的联系，从而导致 AICD 的增加。通过在 CD4 T 细胞激活过程中统一微管细胞骨架和线粒体的组织，这项工作强调了这种连接对于关键的细胞不对称以及糖酵解、线粒体呼吸和细胞活力等代谢功能的重要性。
