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Tissue mechanics controls T-cell activation and metabolism

Kevin P. Meng, Fatemeh S. Majedi, Timothy J. Thauland, Manish J. Butte
doi: https://doi.org/10.1101/581322
Kevin P. Meng
1Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA.
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Fatemeh S. Majedi
2Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
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Timothy J. Thauland
3Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
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Manish J. Butte
3Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
4Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
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SUMMARY

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 18, 2019.
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Tissue mechanics controls T-cell activation and metabolism
Kevin P. Meng, Fatemeh S. Majedi, Timothy J. Thauland, Manish J. Butte
bioRxiv 581322; doi: https://doi.org/10.1101/581322
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Tissue mechanics controls T-cell activation and metabolism
Kevin P. Meng, Fatemeh S. Majedi, Timothy J. Thauland, Manish J. Butte
bioRxiv 581322; doi: https://doi.org/10.1101/581322

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