Abstract

CD47 (integrin associated protei is expressed in immune cells throughout the human body. Prior experiments show CD47 is downregulated for both mRNA and protein in active Multiple Sclerosis (MS) lesions. To assess its role in disease progression, we induced wild-type CD57/B6 mice with EAE. Data showed that mice treated with CD47 antibody at peak of disease exhibited a worsening of disease state with deviation in the cytokine profile. Next, immunohistoochemical studies were performed to decipher the expression of CD47 in three distinct subtypes of lesions: acute plaque, chronic active plaque, and chronic plaque. CD47 was found to be associated with compact myelin in normal tissue of diseases MS brains and decreased in demyelinated tissue of diseased MS brains. It was also expressed in reactive astrocytes and macrophages of both AP and CAP. We followed with in vivo assays of human myelin incubated with activated mouse macophages in the presence of immunoglobulin as a control and CD47 antibody. In line with our hypothesis, results corroborated an increase in phagocytois in cells exposed to the antibody. As CD47 interacts with the SIRPa receptor, a further study was performed using SIRPa antiboy. This too showed increased phagocytosis. A confirmatory ecxperiment was performed using splenocytes, in which similar results were seen. The summation of these findings is that low levels of CD47 attenuate myelin phagocytosis, in turn, worsening demyelination. This study of CD47 exemplifies how a large scale profile can shed mechanistic insights into pathophysiology. While the focus here is on its impact in demyelination, this discovery opens the door to the possibility that CD47 is involved in creation of the packed myelin sheath around the axon. Furthermore, this discovery provides another direction for Multiple Sclerosis therapy.