Stiffness in the tissue microenvironment changes in most diseases and immunological conditions, but its direct influence on the immune system is poorly understood. Here, we show that static tension impacts immune cell function, maturation, and metabolism. Bone-marrow-derived and/or splenic dendritic cells (DCs) grown in vitro at physiological resting stiffness have reduced proliferation, activation, and cytokine production compared with cells grown under higher stiffness, mimicking fibro-inflammatory disease. Consistently, DCs grown under higher stiffness show increased activation and flux of major glucose metabolic pathways. In DC models of autoimmune diabetes and tumor immunotherapy, tension primes DCs to elicit an adaptive immune response. Mechanistic workup identifies the Hippo-signaling molecule, TAZ, as well as Ca²⁺-related ion channels, including potentially PIEZO1, as important effectors impacting DC metabolism and function under tension. Tension also directs the phenotypes of monocyte-derived DCs in humans. Thus, mechanical stiffness is a critical environmental cue of DCs and innate immunity.

在大多数疾病和免疫条件下，组织微环境的刚度会发生变化，但其对免疫系统的直接影响却知之甚少。在这里，我们表明静态张力会影响免疫细胞功能、成熟和新陈代谢。体外生长的骨髓来源和/或脾树突细胞 (DC)与在更高刚度下生长的细胞相比，在生理静息刚度下，增殖、活化和细胞因子产生减少，模拟纤维炎症疾病。一致地，在较高刚度下生长的 DC 显示主要葡萄糖代谢途径的激活和通量增加。在自身免疫性糖尿病和肿瘤免疫治疗的 DC 模型中，张力使 DC 引发适应性免疫反应。机制检查将 Hippo 信号分子 TAZ 以及 Ca ²⁺相关离子通道（包括潜在的 PIEZO1）鉴定为影响 DC 代谢和张力下功能的重要效应物。张力还指导人类单核细胞衍生 DC 的表型。因此，机械刚度是 DC 和先天免疫的关键环境线索。