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

Fischer, R., Padutsch, T., Bracchi-Ricard, V., Murphy, K. L., Martinez, G. F., Delguercio, N., Elmer, N., Sendetski, M., Diem, R., Eisel, U. L. M., Smeyne, R. J., Kontermann, R. E., Pfizenmaier, K. & Bethea, J. R., Oct-2019, In : Brain, Behavior, and Immunity. 81, p. 247-259

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

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DOI

  • 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. Bethea

Tumor 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 treat motor and sensory disease in MS as well as other inflammatory diseases or neuropathic pain conditions.

Original languageEnglish
Pages (from-to)247-259
JournalBrain, Behavior, and Immunity
Volume81
Early online date17-Jun-2019
Publication statusPublished - Oct-2019

    Keywords

  • TNF ligands, TNF receptor superfamily, Multiple sclerose

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