Scientists discover the immune system’s hidden sense of touch

Scientists at McGill University have discovered a surprising ability in immune cells that could reshape our understanding of how the body develops lasting protection against infections.

For years, researchers believed that tissue-resident memory T cells, specialized immune cells that remain in the body's tissues after an infection and respond quickly if the same threat returns, were guided mainly by chemical signals.

However, a new study published in Nature Immunology challenges that assumption. Researchers found that T cells can detect how stiff their surrounding tissues are and use this physical information to influence whether they develop into long-lasting memory cells. The findings suggest that adjusting to the stronger mechanical forces within tissues may be important for these protective cells to survive over time.

"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 research brought together scientists from McGill's Department of Physiology, the Alan Edwards Centre for Research on Pain, the Department of Bioengineering, and the McGill University Health Centre, along with collaborating institutions in the Netherlands and the United States.

Understanding how T cells respond to physical conditions could eventually open new possibilities for treating diseases in which the immune system mistakenly targets healthy tissue. These include autoimmune disorders, allergies, and complications involving transplant rejection.

"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 investigate whether physical surroundings influence T cell behavior, the researchers studied immune cells collected from humans and mice. They placed the cells inside specially designed collagen gels that mimicked tissues with different levels of stiffness.

The experiments revealed a clear pattern. As the gels became stiffer, T cells were increasingly likely to acquire characteristics associated with tissue-resident memory cells, which help provide long-term immune protection.

These results indicate that the physical properties of surrounding tissues can help shape how immune cells develop, adding an important new dimension to scientists' understanding of immune memory.

The researchers now hope to identify the specific molecular sensor that enables T cells to detect their physical environment. Determining how this sensor converts mechanical forces into changes in cell behavior could help explain how the immune system establishes lasting protection.

The study received funding from the Human Frontier Science Program, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Natural Sciences and Engineering Research Council of Canada, and the U.S. National Institutes of Health.