AbstractExplorations of New Key Factors of Immune Cells in Autoimmune Diseases By Demarcus Bunn The work presented in this dissertation demonstrates an emerging role of immune cells in type one diabetes (T1D) and multiple sclerosis (MS). The immune cells that will be presented are neutrophils and T-cells. Presented work shows an altered cell metabolism in both disease states that leads to further secondary complications. An overview of the immunology, as well as each autoimmune disease, will be presented. Experimental efforts to increase or decrease cell metabolism in order to alleviate secondary complications will be shown. Furthermore, the use of 3D printed devices for in vitro models mimicking these disease states properties will be presented.Individuals T1D have a history of being more susceptible to infection. This section of the dissertation will demonstrate how a once forgotten pancreatic peptide, C-peptide, has a positive effect on raising immunity through improving immune cell energetics. Previous studies in the Spence lab have shown that C-peptide only binds to red blood cells (RBC) in the presence of albumin, but for the biological changes, Zn2+ is needed. Spence lab research has shown that the combination of C-peptide/Zn2+/albumin increases the metabolism of RBCs. This work shows novel data showing that C-peptide binds specifically to other cell types. Additionally, changes in cell metabolism will be investigated. This portion of the dissertation is important for alleviating reoccurring and persistent infections.MS is characterized by the destruction of the myelin sheath around the nerves. The cell type that does the damage is T lymphocytes. However, little research has been done investigating what makes the permeability of the blood-brain barrier increase. Here, we will introduce the potential role of NETosis, a form of programmed cell death, has on blood brain barrier permeability. There have been recent reports that exogenous adenosine triphosphate (ATP) increases the rate of NETosis production in vitro. Previous work in the Spence lab has shown that RBCs from individuals with MS secrete significantly more ATP than control red blood cells. Presented work will show that ATP derived directly from RBCs causes dysregulation of NETosis. The concluding section of the dissertation will be dedicated to 3D printing. An overview of the current state and future advancements of 3D printing will be presented. Presented work will show the use of 3D printing to provide more relevant conditions for in vitro experiments. Here, 3D printed models were used to investigate immune cell behaviors and changes in cell bioenergetics.
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