Exogenous activation of tumor necrosis factor receptor 2 promotes recovery from sensory and motor disease in a model of multiple sclerosis

Publication date: Available online 17 June 2019Source: Brain, Behavior, and ImmunityAuthor(s): Roman Fischer, Tanja Padutsch, Valerie Bracchi-Ricard, Kayla L. Murphy, George.F. Martinez, Niky Delguercio, Nicholas Elmer, Maksim Sendetski, Ricarda Diem, Ulrich L.M. Eisel, Richard J. Smeyne, Roland E. Kontermann, Klaus Pfizenmaier, John R. BetheaAbstractTumor necrosis factor receptor 2 (TNFR2) is a transmembrane receptor that promotes immune modulation and tissue regeneration and is recognized as a potential therapeutic target for multiple sclerosis (MS). However, TNFR2 also contributes to T effector cell function and macrophage-TNFR2 recently was shown to promote disease development in the experimental autoimmune encephalomyelitis (EAE) model of MS. We here demonstrate that systemic administration of a TNFR2 agonist alleviates peripheral and central inflammation, and reduces demyelination and neurodegeneration, indicating that protective signals induced by TNFR2 exceed potential pathogenic TNFR2-dependent responses. Our behavioral data show that systemic treatment of female EAE mice with a TNFR2 agonist is therapeutic on motor symptoms and promotes long-term recovery from neuropathic pain. Mechanistically, our data indicate that TNFR2 agonist treatment follows a dual mode of action and promotes both suppression of CNS autoimmunity and remyelination. Strategies based on the concept of exogenous activation of TNFR2 therefore hold great promise as a new therapeutic approach to tre...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research