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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月3日

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  • 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

摘要

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.