When immune cells get recruited to infections, tumors, or other sites of inflammation they exit the blood stream and begin searching for the damage. But how they effectively traverse the body's tissue and home in on their targets is unclear. A new study led by Deborah Fowell, Ph.D. suggests that T cells have distinct navigation systems that help them pinpoint their targets.
Fowell's research team, based in the David H. Smith Center for Vaccine Biology and Immunology in the Department of Microbiology and Immunology made the discovery by visualizing the immune system in real time using intravital multiphoton microscopy. The technology allows you to look directly into the skin and observe the dynamic behavior of immune cells 'live.' Their findings were published earlier this month in the journal Immunity.
"We thought that locating the infection foci was a passive event for immune cells; that they used the tissue as a scaffold to weave their way through this complex matrix to get to their target," said Fowell, Dean's professor in the Department of Microbiology and Immunology. "We discovered that they are pre-programmed to respond to certain cues within the tissue microenvironment that help them find their targets more efficiently."
The team hopes that discovering these specialized programs for migration in tissues will provide new therapeutic targets that enable manipulation of the immune response in a disease-specific or tissue-specific fashion, rather than globally suppressing the immune system. Possibilities include boosting protective immunity in diseases where the immune system is inefficient, such as chronic infections and tumors, and limiting immunity in diseases that are exacerbated by the immune system, like autoimmunity and heart disease.
Hen Prizant, Ph.D., a postdoctoral fellow in Fowell's lab and Alison Gaylo-Moynihan, M.D., Ph.D., a former student in the lab are co-first authors. Graduate students Ninoshka R.J. Fernandes, Hannah Bell, Dillon C. Schrock, Tara Capece, Brandon Walling, and Christopher Anderson contributed to the study. Faculty members David Topham, Minsoo Kim, Alan Smrcka and James Miller are also authors.
Fowell credits the new finding to the power of NIH Program Project Grants (P01), which allow faculty, trainees and students to explore uncharted scientific territory and branch out among different disciplines. For example, the team reached across Elmwood Avenue to have conversations with astrophysicists and engineers on River Campus about how objects move through and are found in space. The P01 that funded the research was awarded to Fowell (PI) and Kim, Topham and Miller in 2014.