Exogenous activation of tumor necrosis factor receptor 2 promotes recovery from sensory and motor disease in a model of multiple sclerosis
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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
17 June 2019
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| In: |
Brain, behavior and immunity
Year: 2019, Volume: 81, Pages: 247-259 |
| ISSN: | 1090-2139 |
| DOI: | 10.1016/j.bbi.2019.06.021 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.bbi.2019.06.021 Verlag: http://www.sciencedirect.com/science/article/pii/S0889159119303782 
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| Author Notes: | 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 |
| Summary: | 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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| Item Description: | Gesehen am 29.10.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1090-2139 |
| DOI: | 10.1016/j.bbi.2019.06.021 |