TY - JOUR T1 - Tissue mechanics controls T-cell activation and metabolism JF - bioRxiv DO - 10.1101/581322 SP - 581322 AU - Kevin P. Meng AU - Fatemeh S. Majedi AU - Timothy J. Thauland AU - Manish J. Butte Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/18/581322.abstract N2 - Upon immunogenic challenge, lymph nodes become mechanically stiff as immune cells proliferate within their encapsulated environments, and with resolution, they reestablish a soft, baseline state. We found that these mechanical changes in the microenvironment promote and then restrict T-cell activation and metabolic reprogramming. Sensing of tissue mechanics by T cells requires the mechanosensor YAP. Unlike in other cells where YAP promotes proliferation, YAP in T cells suppresses proliferation in a stiffness-dependent manner by directly restricting the translocation of NFAT into the nucleus. YAP regulates T-cell responses against viral infections and in autoimmune diabetes. Our work reveals a new paradigm whereby tissue mechanics fine-tunes adaptive immune responses in health and disease.One Sentence Summary Tissue mechanics regulates T cells. ER -