Mechanosensing through YAP controls T cell activation and metabolism

J Exp Med. 2020 Aug 3;217(8):e20200053. doi: 10.1084/jem.20200053.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Active Transport, Cell Nucleus / immunology
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology*
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology*
  • Cell Nucleus / genetics
  • Cell Nucleus / immunology
  • Cell Proliferation*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Lymphocyte Activation*
  • Mechanotransduction, Cellular / genetics
  • Mechanotransduction, Cellular / immunology*
  • Mice
  • Mice, Transgenic
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / immunology
  • T-Lymphocytes / immunology*
  • Virus Diseases / genetics
  • Virus Diseases / immunology
  • YAP-Signaling Proteins


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • NFATC Transcription Factors
  • Nfatc2 protein, mouse
  • YAP-Signaling Proteins
  • Yap1 protein, mouse