Institut Curie Section Recherche, INSERM U932 & PSL Research University, Paris, France.
Laboratoire Matières et systèmes complexes, Université Paris-Diderot and CNRS, UMR 7057, Sorbonne Paris Cité, Paris, France.
Elife. 2017 Jun 8;6:e23190. doi: 10.7554/eLife.23190.
T cells are mechanosensitive but the effect of stiffness on their functions is still debated. We characterize herein how human primary CD4 T cell functions are affected by stiffness within the physiological Young's modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. Yet, upon TCR/CD3 stimulation, while cytokine production increases within a wide range of stiffness, from hundreds of Pa to hundreds of kPa, T cell metabolic properties and cell cycle progression are only increased by the highest stiffness tested (100 kPa). Finally, mechanical properties of adherent antigen-presenting cells modulate cytokine production by T cells. Together, these results reveal that T cells discriminate between the wide range of stiffness values found in the body and adapt their responses accordingly.
T 细胞对机械刺激敏感,但机械刚度对其功能的影响仍存在争议。本文中,我们研究了在生理杨氏模量范围 0.5 kPa 至 100 kPa 内,刚度如何影响人源原代 CD4 T 细胞的功能。刚度可调节 T 淋巴细胞的迁移和 TCR/CD3 触发引起的形态变化。刚度还会增加 TCR 诱导的免疫系统、代谢和细胞周期相关基因。然而,在 TCR/CD3 刺激下,尽管细胞因子的产生在从数百帕斯卡到数百千帕斯卡的广泛刚度范围内增加,但 T 细胞的代谢特性和细胞周期进展仅在测试的最高刚度(100 kPa)下增加。最后,粘附性抗原呈递细胞的力学特性调节 T 细胞产生细胞因子。总之,这些结果表明 T 细胞能够区分体内存在的广泛的刚度值,并相应地调整其反应。