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

• Verfasst von: Fischer, Roman [VerfasserIn]
• Verfasst von: Diem, Ricarda [VerfasserIn]
• Titel: Exogenous activation of tumor necrosis factor receptor 2 promotes recovery from sensory and motor disease in a model of multiple sclerosis
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: 17 June 2019
• Umfang: 13 S.
• Fussnoten: Gesehen am 29.10.2019
• Titel Quelle: Enthalten in: Brain, behavior and immunity
• Ort Quelle: Orlando, Fla. [u.a.] : Elsevier, 1987
• Jahr Quelle: 2019
• Band/Heft Quelle: 81(2019), Seite 247-259
• ISSN Quelle: 1090-2139
• DOI: doi:10.1016/j.bbi.2019.06.021
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: EAE
• Sach-SW: Pain
• Sach-SW: Recovery
• Sach-SW: TNF
• Sach-SW: TNFR2
• K10plus-PPN: 1680554646

Abstract

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.