This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Scientists have long believed that tissue-resident memory T cells—which remain in tissues after an infection has cleared and respond rapidly if the threat returns—are shaped primarily by biochemical signals. A McGill University–led study has now uncovered a previously unknown ability of T cells that could change our understanding of how long-term immunity develops.
The new findings, published in Nature Immunology, reveal that T cells can sense the stiffness of the tissues around them and use these cues to help determine whether they become long-lived memory cells. Researchers suggest adapting to the greater mechanical forces found in tissues may be necessary for memory T cells to survive long term. "This is an exciting fundamental finding that challenges the way we think about immune cells," said lead author Judith Mandl, 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 discovery was made through a collaboration involving researchers from McGill's Department of Physiology, the Alan Edwards Center for Research on Pain, the Department of Bioengineering, the McGill University Health Center and partner institutions in the Netherlands and the United States. The discovery could eventually inform new approaches to treating autoimmune diseases, allergies and transplant rejection, where T cells can mistakenly attack healthy tissue. The findings may also have implications for cancer research, the authors note.
"Tumors are often dense and physically difficult for immune cells to penetrate. Understanding how T cells adapt to these environments could help researchers design cancer immunotherapies that are better able to reach and attack tumors," said Mandl. To test how T cells respond to their environment, immune cells from humans and mice were placed in engineered collagen gels that replicated tissues of varying stiffness.
The stiffer the gel, the more likely the cells were to develop into cells resembling tissue-resident memory cells, which are associated with long-term immune protection. Researchers say their next challenge is identifying the molecular sensor that allows T cells to feel their environment and translate physical force into biological change. Jérémy Postat et al, Mechanosensing by T cells promotes a tissue-resident memory transcriptional program, Nature Immunology (2026).
DOI: 10.1038/s41590-026-02581-9 BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021.
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