Immune cells can sense tissue stiffness, shaping long-term immunity

Scientists at McGill University have discovered that T cells possess a previously unknown ability to sense the mechanical stiffness of surrounding tissues. The study, published in Nature Immunology, shows that this mechanosensing capability influences whether T cells develop into tissue-resident memory cells, which provide rapid, long-term immune protection after an infection clears.

For decades, researchers believed that biochemical signals alone directed the formation of these memory cells. The new findings demonstrate that physical forces in the tissue environment act as an active factor in shaping T cell behavior and fate.

In experiments using engineered collagen gels that mimicked tissues of varying stiffness, immune cells from both humans and mice were more likely to adopt a memory-like state when placed in stiffer environments. The stiffer gels also altered cell morphology, reduced motility, and increased expression of nuclear lamin A/C, a protein linked to mechanical sensing.

Lead author Judith Mandl, a professor in McGill's Department of Physiology, described the finding as a fundamental shift in understanding immune cells. The research involved collaborators from McGill's Department of Bioengineering, the Alan Edwards Center for Research on Pain, the McGill University Health Centre, and partner institutions in the Netherlands and the United States.

The discovery opens new research avenues for conditions where T cells malfunction, such as autoimmune diseases, allergies, and transplant rejection. It may also inform cancer immunotherapy, as tumors are often dense and physically difficult for immune cells to penetrate; understanding how T cells adapt to mechanical barriers could help design therapies that better reach and attack tumors.

The researchers' next step is to identify the specific molecular sensor that allows T cells to translate physical force into biological changes. Pinpointing this mechanism could enable targeted interventions to modulate immune responses in a range of diseases.