Altered copper homeostasis impacts immune development and function 4636

Abstract Description Copper is essential for all living organisms and required by proteins involved in oxidative stress maintenance, mitochondrial metabolism, and cellular signaling pathways. However, excess copper is toxic. In humans, copper imbalance can occur due to malnutrition, cancer, autoimmune disease, or mutations in copper transporters. While copper deficiency impairs neutrophil and macrophage function, the mechanisms through which copper regulates immune development and immune cell function are not well understood. Thus, we used models of genetic or dietary-induced copper imbalance to examine the impacts of altered copper homeostasis on immune development, activation, and function. We first evaluated whether changes in copper availability impact developing and mature immune cell populations in mouse models. We found that modified copper availability shifted populations of developing thymocytes, as well as circulating innate and adaptive immune cells. As copper is required for signaling and metabolic pathways critical to lymphocyte activation, we also investigated whether copper availability alters lymphocyte activation in cell culture or in the context of a murine viral infection. Our results demonstrate that dysregulated copper homeostasis directly affects lymphocyte activation and the host response to viral infection. Overall, our findings will improve our understanding of how copper regulates specific immune cell populations during the development of an effective immune response. Funding Sources Supported by NIH 5T32AI106700-07 and American Lebanese Syrian Associated Charities. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)