Project 454472

Immune cells known as T lymphocytes, or T cells, are responsible for identifying and clearing infected cells from our bodies. To effectively respond to an infection, T cells require enough energy and building materials to support their growth, proliferation, and effector function. To meet this demand, T cells reprogram their metabolism. For example, T cells consume high amounts of glucose in response to infection and metabolize (break down or modify) it to produce other products. However, it is unclear which of these glucose-derived products are required by T cells and how these products influence T cell function. We recently identified that, of all the glucose-derived products, uridine diphosphate glucose (UDP-Glc) is the most abundant in activated T cells. Our hypothesis is that activated T cells rely on UDP-Glc, and that modulating UDP-Glc levels within T cells or their environment can impact T cell function. We propose to use both in vitro and in vivo experimental systems to study the fate of UDP-Glc in activated T cells and the consequences of depleting UDP-Glc on T cell responses to infection. Our ultimate goal is to determine whether manipulating UDP-Glc metabolism is a suitable therapeutic avenue to optimize immune responses against infections, autoimmune diseases, and cancer.