Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex
Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex
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DOI：
10.7554/elife.55995
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发表时间：
2020-07-27
期刊：
影响因子：
7.7
通讯作者：
Burkhardt, Janis K.
中科院分区：
文献类型：
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作者：
Blumenthal, Daniel;Chandra, Vidhi;Burkhardt, Janis K.
树突状细胞(DC)激活T细胞涉及T细胞肌动蛋白细胞骨架施加的力，而T细胞肌动蛋白细胞骨架与相互作用的抗原提呈细胞的皮质骨架相反。在免疫反应中，树突状细胞经历一个成熟的过程，优化他们有效地启动幼稚T细胞的能力。使用原子力显微镜，我们发现在成熟过程中，DC皮质硬度通过涉及肌动蛋白聚合的过程而增加。使用刺激性水凝胶和表达突变细胞骨架蛋白的DC，我们发现增加僵硬度可以降低T细胞激活所需的激动剂剂量。CD4(+)T细胞比CD8(+)T细胞表现出更深层次的僵硬依赖性。最后，当用pMHC而不是抗CD3 epsilon刺激T细胞时，僵硬反应最强劲，这与涉及受体变形的机械传感机制一致。综上所述，我们的数据显示，与成熟相关的细胞骨架变化改变了DC的生物物理特性，提供了共刺激T细胞激活的机械信号。
T cell activation by dendritic cells (DCs) involves forces exerted by the T cell actin cytoskeleton, which are opposed by the cortical cytoskeleton of the interacting antigen-presenting cell. During an immune response, DCs undergo a maturation process that optimizes their ability to efficiently prime naive T cells. Using atomic force microscopy, we find that during maturation, DC cortical stiffness increases via a process that involves actin polymerization. Using stimulatory hydrogels and DCs expressing mutant cytoskeletal proteins, we find that increasing stiffness lowers the agonist dose needed for T cell activation. CD4(+) T cells exhibit much more profound stiffness dependency than CD8(+) T cells. Finally, stiffness responses are most robust when T cells are stimulated with pMHC rather than anti-CD3 epsilon, consistent with a mechanosensing mechanism involving receptor deformation. Taken together, our data reveal that maturation-associated cytoskeletal changes alter the biophysical properties of DCs, providing mechanical cues that costimulate T cell activation.