The role of tumor necrosis factor receptor 2 (TNFR2) in EAE

Abstract Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system which affects over 2 million people worldwide and most common neurological disability in young adults. MS heterogenous characterized by recurrent, remitting and/or progressive deficits, clinical manifestations include nerve damage, visual loss, motor balance impairment, gait disturbance, others. While several environmental genetic risk factors have been identified, such as DR2b (DRB1*1501) human MHC class II allele, molecular mechanisms underlying development severity remain poorly understood. Tumor necrosis factor cytokine that exerts its effects through two different surface receptors TNFR1 TNFR2, it has identified key player pathogenesis. TNFR2 thought to protective role experimental encephalomyelitis (EAE), mouse model for MS, altering function astrocytes regulatory T cells (Tregs). Previous data from our lab demonstrated absence transgenic mice expressing allele lacking (DR2bDR2) develop more severe form EAE, exhibiting astrogliosis. We previously multiple Treg-associated genes were upregulated CD4 +T DR2bDR2 compared those control mice. However, exact mechanism regulates Treg EAE unknown. Here, we show deletion impacts ability Tregs expand vitro well their localization within brains undergoing EAE. Our results provide insights into limits protects against CNS inflammation.