Mechanosensing through YAP controls T cell activation and metabolism
Open Access
- 1 August 2020
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 217 (8)
- https://doi.org/10.1084/jem.20200053
Abstract
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.Funding Information
- Stanford Shared FACS Facility
- UCLA Jonsson Comprehensive Cancer Center
- National Institutes of Health (P30 CA016042, 5P30 AI028697)
- UCLA Metabolomics
- National Institutes of Health (R01 GM110482)
- UCLA Jonsson Comprehensive Cancer Center (P30CA016042)
- Stanford Child Health Research Institute
- UCLA Children’s Discovery and Innovation Institute
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