Mechanosensing through YAP controls T cell activation and metabolism

Kevin P Meng; Fatemeh S Majedi; Timothy J Thauland; Manish J Butte

doi:10.1084/jem.20200053

Mechanosensing through YAP controls T cell activation and metabolism

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

Authors

Kevin P Meng¹, Fatemeh S Majedi², Timothy J Thauland³, Manish J Butte^{3

4}

Affiliations

¹ Department of Microbiology and Immunology, Stanford University, Stanford, CA.
² Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA.
³ Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA.
⁴ Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA.

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.

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding