Autophagy is the cellular equivalent of trash pickup and recycling — it is a process by which proteins, protein aggregates and damaged cellular organelles are degraded in order to reuse nutrients and promote cellular metabolism.
Now researchers at Vanderbilt University Medical Center have found that autophagy also plays an important role in priming the body’s immune system.
Vps34 is an enzyme found in all cells in higher organisms. Usually it helps transport cellular proteins for degradation and disposal, but its role is more complex in dendritic cells of the skin and inner lining of the nose, lungs, stomach and intestines.
Dendritic cells are the body’s early warning system. Their main job is to process and present foreign antigens, protein “nametags” worn by invading bacteria or viruses, for example, to T lymphocytes, which then respond to control the infection.
Reporting this week in the Proceedings of the National Academy of Sciences, Luc Van Kaer, Ph.D., and colleagues generated a strain of mice in which the gene for Vps34 was specifically “knocked out” in dendritic cells.
These animals displayed defects in the survival and function of a subset of dendritic cells that normally present antigens to T cells. This may have important implications for targeting the Vps34 pathway for therapeutic purposes.
In particular, targeting Vps34 to inhibit autophagy had been considered as an anticancer therapy. Because autophagy protects cancer cells against metabolic stress, blocking it may make them less likely to develop resistance to chemotherapy and radiation therapy.
However the current study suggests that inhibition may lead to impaired T-cell-mediated immunity, the researchers conclude.
First author Vrajesh Parekh, Ph.D., former research assistant professor at Vanderbilt, is currently a senior scientist at Pfizer. Van Kaer is the Elizabeth and John Shapiro Professor and professor of Microbiology, Pathology and Immunology.
The research was supported in part by National Institutes of Health grants CA068485, DK058404, DK104817, DK081536 and NS064090.