Grant: Project Grant

Tissue-resident memory (TRM) cells are a group of immune cells that stay in tissues like the skin, lungs, and intestines, ready to respond quickly to infections. These cells are best known for remembering past infections and launching a targeted attack when the same pathogen returns. However, they can also react without recognizing a specific pathogen-responding instead to general signals of infection or tissue damage. While this ability can help protect the body, it must be carefully controlled to avoid harmful inflammation or autoimmune diseases. Our previous studies using a mouse model of intestinal parasite infection discovered that TRM cells were the main producers of a protein that acts on surrounding cells to increase immune defense. Surprisingly, these TRM cells did not need to recognize a specific pathogen to have this effect. Instead, their activation depended on signals from the gut microbiome and, in turn, helped limit tissue damage and maintain gut function but did not directly affect parasite levels. This suggests that TRM cells play an important role in protecting tissues during infection, not just fighting off pathogens. In this proposal, we aim to reveal the specific signals that optimize TRM cell function to help maintain tissue health during infections. Results from our studies will inform strategies to improve immune-based therapies for diverse illnesses ranging from infection disease to cancer.