Mechanosensing by T cells promotes a tissue-resident memory transcriptional program.

Authors

Jérémy Postat, Mauricio Merino, Angela R Mingarelli, Aysha Cerf, Aanya Bhagrath, Dhanesh Patel, Connie Shen, Johanna Brodbeck, Pouria Tirgar, Dakota Rogers, Jules Blanc, Thiviya Jeyakumar, Caitlin Schneider, Shana Coley, Nadia Giannetti, Taylor A DePauw, Johannes Textor, Allen Ehrlicher, Stephen C Jameson, Reza Sharif-Naeini, Abhinav Sharma, Judith N Mandl

Published in

Nature immunology. Jul 03, 2026. Epub Jul 03, 2026.

Abstract

Cell migration and strategic positioning within tissues is critical for the rapid mobilization of a T cell response. T cells must remain motile in both lymphoid and nonlymphoid tissues, which vary widely in mechanical properties such as stiffness. Here we showed that activated T cells sensed mechanical cues and responded with changes in cell morphology, nuclear envelope composition and initiation of DNA repair to protect their genomic material from force-mediated damage. Increased mechanical input also drove the transcriptional reprogramming of activated T cells, including changes in many of the core genes shared by tissue-resident memory T cells across diverse tissues, by modulating the expression of the tissue-resident memory T cell-associated transcription factors Klf2, Runx3 and Hic1. Thus, mechanosensing by activated T cells impacted T cell fate, promoting a transcriptional program associated with tissue residency.

PMID:
42399696
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.

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