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

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• T cell migration is crucial for immune responses in various tissues.
• Tissues possess diverse mechanical properties like stiffness that can influence cell behavior.

Purpose of the Study:

• To investigate how activated T cells perceive and respond to mechanical cues from their environment.
• To understand the impact of mechanical sensing on T cell morphology, genome stability, and transcriptional programming.

Main Methods:

• Analysis of T cell responses to varying mechanical stiffness.
• Assessment of changes in cell morphology, nuclear envelope composition, and DNA repair mechanisms.
• Transcriptional profiling to identify key gene expression changes.

Main Results:

• Activated T cells alter morphology, nuclear envelope, and initiate DNA repair in response to mechanical input.
• Increased mechanical forces drive transcriptional reprogramming in T cells.
• Modulation of transcription factors Klf2, Runx3, and Hic1 influences tissue-resident memory T cell gene expression.

Conclusions:

• Mechanosensing by T cells is vital for adapting to tissue microenvironments.
• Mechanical cues influence T cell fate decisions, promoting a transcriptional program associated with tissue residency.