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bioRxiv · 10.1101/581322

Tissue mechanics controls T-cell activation and metabolism

Meng, K.·Majedi, F. S.·Thauland, T. J.·Butte, M.
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Abstract

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.\n\nOne Sentence SummaryTissue mechanics regulates T cells.

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Meng, K., Majedi, F. S., Thauland, T. J., Butte, M.. 2019-03-18. Tissue mechanics controls T-cell activation and metabolism. https://doi.org/10.1101/581322

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