Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 217, Issue 8, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20200053
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Funding
- National Institutes of Health [R01 GM110482, P30 CA016042, 5P30 AI028697]
- UCLA Metabolomics core
- UCLA Jonsson Comprehensive Cancer Center [P30CA016042]
- Stanford Child Health Research Institute
- UCLA Children's Discovery and Innovation Institute
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Upon immunogenic challenge, lymph nodes become mechanically stiff as immune cells activate and proliferate within their encapsulated environments, and with resolution, they reestablish a soft baseline state. Here we show that sensing these mechanical changes in the microenvironment requires the mechanosensor YAP. YAP is induced upon activation and suppresses metabolic reprogramming of effector T cells. Unlike in other cell types in which YAP promotes proliferation, YAP in T cells suppresses proliferation in a stiffness-dependent manner by directly restricting the translocation of NFAT1 into the nucleus. YAP slows T cell responses in systemic viral infections and retards effector T cells in autoimmune diabetes. Our work reveals a paradigm whereby tissue mechanics fine-tune adaptive immune responses in health and disease.
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