The role of astrocyte TNFR2 in experimental autoimmune encephalomyelitis 4321

Abstract Description Multiple Sclerosis (MS) is a chronic autoimmune, neuroinflammatory, and neurodegenerative disease of the central nervous system characterized by immune dysregulation, demyelination, axonal damage, and neuron loss. Astrocytes influence critical aspects of MS pathogenesis including immune cell infiltration, neuroinflammation, demyelination and remyelination. In MS, tumor necrosis factor (TNF) levels are elevated in the cerebrospinal fluid, suggesting a role in the disease process. Previous research from our lab using a whole-body TNFR2 knockout mouse line revealed a role for TNFR2 signaling in limiting proinflammatory astrocyte functions. Still, the role of TNFR2 signaling specifically in astrocytes in EAE/MS remains unclear. Here, we investigate the role of TNFR2 in astrocytes using a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). We utilized an inducible astrocyte-specific TNFR2 knockout mouse line for our studies. We found that deletion of TNFR2 specifically in astrocytes resulted in reduced EAE severity, CD4+ T cell infiltration, and total astrocyte number. Furthermore, investigation of pathology-associated transcription and cytokine production in TNFR2-deficient astrocytes suggested pathways involving astrocyte proliferation and immune cell infiltration. Collectively, our work indicates that TNFR2 can have protective functions when expressed in certain cell types, but TNFR2 signaling in astrocytes may have disease-promoting functions in EAE/MS. Funding Sources This research was supported by NIH grant R01NS117742 and support from the Jesse H. & Mary Jones Gibbs Endowed Chair. Topic Categories Neuroimmunology (NEUR)