Characterizing the role of Blimp-1 in regulating encephalitogenic T cells in CNS autoimmunity (IRC8P.483)

Abstract

Abstract Effector and recall responses of T cells play an important role in the pathogenesis of Multiple Sclerosis and EAE. B lymphocyte induced maturation protein-1 (Blimp-1) is a transcription factor that plays important roles in regulating immunity. However, its role in regulating encephalitogenic T cells in EAE has not been characterized. Using YFP/Blimp-1 reporter mice, we analyzed Blimp-1 expression in myelin-specific CD4 T cells in vitro and in vivo. Blimp-1 expression correlates with the encephalitogenicity of myelin-specific CD4 T cells, which is highly expressed in encephalitogenic Th1 and Th17 cells, but not in non-encephalitogenic Th17 cells. Moreover, Blimp-1 is highly expressed in myelin-specific CD4 T cells in the draining lymph nodes, spleen and CNS during EAE development, specifically in activated CD44+IL7Rα+CD4 T cells. As IL-23 significantly enhances the encephalitogenicity of myelin-specific CD4 T cells, we determined if IL-23 upregulates Blimp-1 expression. Our data showed that exogenous IL-23 significantly enhances Blimp-1 expression in myelin-specific CD4 T cells and Blimp-1 is highly expressed in IFNγ+, IL-17+ and IFNγ+ and IL-17 double positive cells in draining LN cells, splenocytes and CNS infiltrating cells. In addition, we determined the role of Blimp-1 in regulating T cell migration and EAE development. Together, our findings suggest that Blimp-1 might play an important role in regulating autoreactive T cells and the development of CNS autoimmunity.