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.
%0 Journal Article
%1 Fischer2019
%A Fischer, Roman
%A Padutsch, Tanja
%A Bracchi-Ricard, Valerie
%A Murphy, Kayla L.
%A Martinez, George.F.
%A Delguercio, Niky
%A Elmer, Nicholas
%A Sendetski, Maksim
%A Diem, Ricarda
%A Eisel, Ulrich L.M.
%A Smeyne, Richard J.
%A Kontermann, Roland E.
%A Pfizenmaier, Klaus
%A Bethea, John R.
%D 2019
%J Brain, Behavior, and Immunity
%K 2019 izi kontermann pfizenmaier
%R 10.1016/j.bbi.2019.06.021
%T Exogenous activation of tumor necrosis factor receptor 2 promotes recovery from sensory and motor disease in a model of multiple sclerosis
%U http://www.ncbi.nlm.nih.gov/pubmed/31220564
%X 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.
@article{Fischer2019,
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.},
added-at = {2019-07-04T08:57:58.000+0200},
author = {Fischer, Roman and Padutsch, Tanja and Bracchi-Ricard, Valerie and Murphy, Kayla L. and Martinez, George.F. and Delguercio, Niky and Elmer, Nicholas and Sendetski, Maksim and Diem, Ricarda and Eisel, Ulrich L.M. and Smeyne, Richard J. and Kontermann, Roland E. and Pfizenmaier, Klaus and Bethea, John R.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/22a4a4faf043423b65d04fdeefb7d38eb/cristiano},
doi = {10.1016/j.bbi.2019.06.021},
interhash = {7b458438891e4684a801a4ac8458da27},
intrahash = {2a4a4faf043423b65d04fdeefb7d38eb},
issn = {08891591},
journal = {Brain, Behavior, and Immunity},
keywords = {2019 izi kontermann pfizenmaier},
month = jun,
pmid = {31220564},
timestamp = {2019-07-04T06:57:58.000+0200},
title = {{Exogenous activation of tumor necrosis factor receptor 2 promotes recovery from sensory and motor disease in a model of multiple sclerosis}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/31220564},
year = 2019
}
