Scientists at McGill University have found that tissue-resident memory T cells can detect the stiffness of the tissue around them, using this physical information to influence whether they develop into long-lasting immune cells. The discovery challenges the long-held view that these cells are guided mainly by chemical signals and could offer new insights into durable protection against infections, cancer immunotherapy, autoimmune disease and transplant complications.
Tissue-resident memory T cells are specialized immune cells that remain in body tissues after an infection and respond rapidly if the same threat appears again. Researchers have traditionally focused on chemical signals as the main factors guiding their development and behavior.
The new study indicates that mechanical forces also play an important role. T cells appear to “feel” the stiffness of their surroundings and adapt to it, potentially helping them survive for longer in tissues where stronger mechanical forces are present.
“This is an exciting fundamental discovery that challenges the way we think about immune cells,” said lead author Judith Mandle, a professor in McGill University’s Department of Physiology. “This suggests that T cells ‘feel’ and adapt to their surroundings, and that the physical environment is an active force shaping T cell behavior.”
The research involved scientists from McGill University’s Department of Physiology, Alan Edwards Pain Research Center, Department of Bioengineering and McGill University Health Center, along with partner institutions in the Netherlands and the United States.
Potential implications for cancer and immunotherapy
Learning how T cells respond to physical conditions could eventually lead to new approaches for treating diseases in which the immune system mistakenly attacks healthy tissue. These include autoimmune diseases, allergies and complications associated with transplant rejection.
The findings may also have implications for cancer research, particularly for treatments that harness the immune system to fight tumors.
“Tumors are dense and often physically difficult for immune cells to invade. Understanding how T cells adapt to these environments could help researchers design cancer immunotherapies that can more effectively reach and attack tumors,” Mandl said.
Testing the physical environment of immune cells
To investigate whether tissue mechanics influence T cell behavior, the researchers studied immune cells from humans and mice. They placed the cells in a specially designed collagen gel that mimics tissues with different levels of stiffness.
The experiments revealed a consistent pattern: as the gel became stiffer, the T cells were increasingly likely to acquire properties associated with tissue-resident memory cells, which provide long-term immune protection.
The results suggest that the physical properties of surrounding tissue can help shape immune-cell development, adding a potentially important dimension to scientists’ understanding of immune memory.
Searching for the cells’ mechanical sensors
The researchers now hope to identify the specific molecular sensors that enable T cells to detect their physical surroundings. Understanding how these sensors translate mechanical forces into changes in cellular behavior could help explain how the immune system establishes durable protection.
The research was funded by 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 National Institutes of Health.
Source: www.sciencedaily.com
