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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
Journal article   Open access   Peer reviewed

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

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, …
Brain, behavior, and immunity, v 81, pp 247-259
Oct 2019
DOI: https://doi.org/10.1016/j.bbi.2019.06.021
PMID: 31220564
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.bbi.2019.06.021View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

EAE Pain Recovery TNF TNFR2
•Systemic TNFR2 agonist treatment promotes long-term recovery.•Systemic TNFR2 agonist therapy follows a dual mode of action in EAE.•TNFR2 agonist-treated mice show reduced systemic and peripheral inflammation.•TNFR2 agonism promotes Treg expansion and OPC proliferation and differentiation. 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.

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33 citations in Web of Science
32 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Neurosciences
Psychiatry
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