Scientists at McGill University have found that tissue-resident memory T cells may use the physical stiffness of surrounding tissue—not just chemical signals—to determine whether they develop into long-lasting immune cells. The discovery suggests that the mechanical environment inside tissues could play an important role in durable protection against infection and may eventually inform treatments for cancer, autoimmune diseases, allergies and transplant-related complications.
Tissue-resident memory T cells are specialized immune cells that remain in the body’s tissues after an infection. If the same threat returns, they can respond rapidly. Researchers have traditionally believed that these cells are guided primarily by chemical signals.
However, a new study published in Innate Immunology challenges that assumption. The researchers found that T cells can detect the stiffness of surrounding tissue and use this physical information to influence whether they develop into long-lasting memory cells. Adapting to stronger mechanical forces within tissues may therefore be important to the long-term survival of these protective cells.
“This is an exciting fundamental discovery that challenges the way we think about immune cells,” said lead author Judith Mandle, a professor in McGill’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 study brought together scientists from McGill University’s Department of Physiology, the Alan Edwards Pain Research Center, the 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
Understanding how T cells respond to physical conditions could eventually open new approaches for treating diseases in which the immune system mistakenly attacks healthy tissue. These include autoimmune diseases, allergies and complications involving transplant rejection.
The finding could also have implications for cancer research, particularly efforts to improve 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.
How researchers studied T cells’ physical sensing
To investigate whether the physical environment influences T cell behavior, the researchers studied immune cells from humans and mice. They placed the cells in a specially designed collagen gel that mimics tissue with varying levels of stiffness.
The experiments revealed a clear pattern: as the gel became stiffer, T cells were increasingly likely to acquire properties associated with tissue-resident memory cells, which provide long-term immune protection.
The results indicate that the physical properties of surrounding tissue can help shape immune-cell development, adding a potentially important dimension to scientists’ understanding of immune memory.
Researchers now hope to identify the specific molecular sensors that enable T cells to detect their physical environment. Determining 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