Researchers report in Nature Immunology that T cells respond to the physical stiffness of their surroundings, challenging the view that chemical signals alone guide immune memory.
Scientists at McGill University say immune cells have an ability that was not previously appreciated: T cells can detect how stiff the tissue around them is. The work, published in Nature Immunology and led by Judith Mandl, a professor in McGill's Department of Physiology, focuses on tissue-resident memory T cells, specialised cells that stay in the body's tissues after an infection and respond quickly if the same threat returns. For years, researchers had believed these cells were guided mainly by chemical signals.
To test whether physical surroundings matter, the team studied immune cells collected from humans and mice and placed them in specially designed collagen gels that mimicked tissues of different stiffness. According to the university's account, the pattern was clear: as the gels became stiffer, the T cells were increasingly likely to acquire characteristics associated with tissue-resident memory cells. The researchers interpret this as a sign that adapting to the stronger mechanical forces inside tissues may help these protective cells survive over time. The experiments were carried out on cells in the laboratory, not in patients.
Mandl described the result as a fundamental finding suggesting that T cells can feel their surroundings and adapt to them. The group now hopes to identify the specific molecular sensor that lets the cells detect their physical environment. The researchers say that understanding this could eventually inform work on autoimmune disorders, allergies and transplant rejection, as well as cancer immunotherapies, since tumours are often dense and hard for immune cells to penetrate. These are stated hopes rather than demonstrated treatments, and further research would be needed before any clinical application. The study drew funding from the Human Frontier Science Program, Canadian research agencies and the U.S. National Institutes of Health.
