Immune Cells Sense Tissue Stiffness to Decide Whether They Become Long-Term Memory Cells

Scientists have long thought that tissue-resident memory T cells - immune cells that stay behind in tissue after an infection clears and respond quickly if it returns - are shaped mainly by chemical signals. A study led by McGill University, published in Nature Immunology, has found that these T cells can also sense the physical stiffness of the tissue around them, and use that mechanical cue to help decide whether they become long-lived memory cells.

"This is an exciting fundamental finding that challenges the way we think about immune cells," said lead author Judith Mandl, a professor in McGill's Department of Physiology. "It suggests T cells can 'feel' their surroundings and adapt to them, making the physical environment an active force in shaping their behavior." The work involved researchers from McGill's Department of Physiology, the Alan Edwards Centre for Research on Pain, the Department of Bioengineering, the McGill University Health Centre, and partner institutions in the Netherlands and the United States.

To test the effect, the researchers placed immune cells from humans and mice into engineered collagen gels built to mimic tissues of different stiffness. The stiffer the gel, the more likely the T cells were to develop into cells resembling tissue-resident memory cells, which provide long-term immune protection. The team says its next step is to identify the molecular sensor that lets T cells feel their environment and convert that physical force into a biological change.

The discovery could eventually inform new treatments for autoimmune diseases, allergies, and transplant rejection, conditions in which T cells mistakenly attack healthy tissue. Mandl noted that tumors are often dense and physically difficult for immune cells to penetrate, and that understanding how T cells adapt to stiff environments could help researchers design cancer immunotherapies better able to reach and attack tumors.