Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 21, Pages E4175-E4183Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1614291114
Keywords
mechanobiology; T-cell activation; microtubule; actin; myosin II
Categories
Funding
- National Science Foundation [1206060, 1607645]
- Direct For Mathematical & Physical Scien
- Division Of Physics [1607645] Funding Source: National Science Foundation
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T-cell receptor (TCR) triggering and subsequent T-cell activation are essential for the adaptive immune response. Recently, multiple lines of evidence have shown that force transduction across the TCR complex is involved during TCR triggering, and that the T cell might use its force-generation machinery to probe the mechanical properties of the opposing antigen-presenting cell, giving rise to different signaling and physiological responses. Mechanistically, actin polymerization and turnover have been shown to be essential for force generation by T cells, but how these actin dynamics are regulated spatiotemporally remains poorly understood. Here, we report that traction forces generated by T cells are regulated by dynamic microtubules (MTs) at the interface. These MTs suppress Rho activation, nonmuscle myosin II bipolar filament assembly, and actin retrograde flow at the T-cell-substrate interface. Our results suggest a novel role of the MT cytoskeleton in regulating force generation during T-cell activation.
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