Exploring the Impact of TNFR2 on Regulatory T Cells and Astrocytes in Experimental Autoimmune Encephalomyelitis (EAE)

Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system which affects over 2 million people worldwide. MS is a heterogenous disease characterized by recurrent, remitting and/or progressive neurological deficits, and clinical manifestations include nerve damage, visual loss, motor and balance impairment, gait disturbance, pain, and others. While several environmental and genetic risk factors have been identified, such as having the human leukocyte antigen DR2b (DRB1*15:01) haplotype, the molecular mechanisms underlying the development and severity of MS remain poorly understood. Tumor necrosis factor (TNF) is a cytokine that exerts its effects through two different surface receptors TNFR1 and TNFR2, and it has been identified as a key player in MS pathogenesis. TNFR2 is thought to have a protective role in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. However, TNFR2 role in health and disease remains controversial and incompletely understood. Previous data from our lab demonstrated that in the absence of TNFR2, transgenic mice expressing the DR2b allele develop a more severe and progressive form of EAE, exhibiting astrogliosis. Using our transgenic TNFR2 knock out model, we were able to explore TNFR2 influence on gene expression in CD4+ T cells and astrocytes, and to functionally and phenotypically characterize TNFR2 deficient Tregs. Additionally, we were able to optimize a way to identify gene and protein expression within mice brain to further determine the presence and characteristics of reactive astrocytes in our mice models during EAE. Our results provide key insights into the mechanism by which TNFR2 regulates Treg and astrocyte function in the context of EAE.