Metabolomics

Biography

Biography: Chia-Lin Hsu

Abstract

Immunometabolism is a new term describing the interactions between metabolism and immunity, the biological functions that have long considered as two distinct entities. However, despite the substrate to be pathogens or nutrients, both processes work to restoring the homeostasis of the body. With modern diet, the correlation between overnutrition and chronic inflammation brings the attention to how metabolic homeostasis contribute to properly controlled immune system. It is becoming clear that immune activation can affect metabolism while metabolic changes also have profound influence on immunological functions. Nevertheless, the molecular mechanisms that connect these two systems are still unclear. For example, lysosomal storage diseases (LSDs) are a group of heterogeneous disorders caused by defects in lysosomal enzymes or transporters, resulting in accumulation of un-degraded macromolecules or metabolites. This accumulation disrupts the cell's normal functioning and gives rise to the clinical manifestations of LSDs. We found that equilibrative nucleoside transporter 3 (ENT3) is a lysosomal specific nucleoside transporter that highly expresses in macrophages. Mice lacking ENT3 developed a spontaneous and progressive macrophage-dominated histiocytosis. In the absence of ENT3, defective apoptotic cell clearance led to lysosomal nucleoside buildup, elevated intralysosomal pH, and altered macrophage function. These studies suggest a cellular and molecular basis for the development of histiocytosis in several human syndromes associated with ENT3 mutations and potentially other LSDs. Furthermore, we will discuss potential roles of ENT3 in other aspects of immune response.