Grant: Operating Grant

Macrophages and dendritic cells are cells of the immune system known as phagocytes (meaning "eating cells"). They are named for their ability to engulf particulate material by a process called phagocytosis. Following phagocytosis, the engulfed material is broken down within compartments known as phagosomes. This process has a diverse range of functions in normal growth and development, but also has a critical role in our body's immune defense system. When macrophages and dendritic cells phagocytose (eat) microorganisms, they break down their proteins (also called antigens) in their phagosomes into small pieces that can be recognized by other cells. The macrophages and dendritic cells then show these pieces of antigen to T-cells, triggering a powerful immune reaction that our body can remember. This is important in our defense against foreign organisms, as well as in disease where our immune system mistakes our own cells as invaders (such as in autoimmunity). Despite their pivotal role, there are fundamental gaps in our understanding of how phagosomes function. We have evidence that a particular chemistry within the phagosome, known as the redox potential, influences how macrophages and dendritic cells digest protein antigens. We think that this can control which parts of an antigen are presented and could have consequences to subsequent events in acquired immunity. In particular, in many autoimmune diseases, which piece of an antigen is presented is critical to how our body reacts. This proposal aims to further understand how the redox potential affects the way phagosomes process antigen, and in turn, how it influences which parts of the antigen are presented. This basic scientific research is broad reaching as it has the potential to profoundly impact human health. In addition to better understanding how our immune system works, this work may lead to different strategies in the management of autoimmune diseases such as rheumatoid arthritis.