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Anti-TNFR1 targeting in humanized mice ameliorates disease in a model of multiple sclerosis.

Williams, Sarah K.; Fairless, Richard; Maier, Olaf; Liermann, Patricia C.; Pichi, Kira; Fischer, Roman; Eisel, Ulrich L. M.; Kontermann, Roland; Herrmann, Andreas; Weksler, Babette; Romero, Nacho; Couraud, Pierre-Olivier; Pfizenmaier, Klaus and Diem, Ricarda (2018). Anti-TNFR1 targeting in humanized mice ameliorates disease in a model of multiple sclerosis. Scientific reports, 8 pp. 1–14.

DOI (Digital Object Identifier) Link: https://doi.org/10.1038/s41598-018-31957-7
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Abstract

Tumour necrosis factor (TNF) signalling is mediated via two receptors, TNF-receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2), which work antithetically to balance CNS immune responses involved in autoimmune diseases such as multiple sclerosis. To determine the therapeutic potential of selectively inhibiting TNFR1 in mice with experimental autoimmune encephalomyelitis, we used chimeric human/mouse TNFR1 knock-in mice allowing the evaluation of antagonistic anti-human TNFR1 antibody efficacy. Treatment of mice after onset of disease with ATROSAB resulted in a robust amelioration of disease severity, correlating with reduced central nervous system immune cell infiltration. Long-term efficacy of treatment was achieved by treatment with the parental mouse anti-human TNFR1 antibody, H398, and extended by subsequent re-treatment of mice following relapse. Our data support the hypothesis that anti-TNFR1 therapy restricts immune cell infiltration across the blood-brain barrier through the down-regulation of TNF-induced adhesion molecules, rather than altering immune cell composition or activity. Collectively, we demonstrate the potential for anti-human TNFR1 therapies to effectively modulate immune responses in autoimmune disease.

Item Type: Journal Item
ISSN: 2045-2322
Extra Information: ** From PubMed via Jisc Publications Router.
** History: received 30-04-2018;
accepted 30-08-2018.
Keywords: Multiple sclerosis; Neuroimmunology
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 56772
SWORD Depositor: Jisc Publications-Router
Depositing User: Jisc Publications-Router
Date Deposited: 28 Sep 2018 11:18
Last Modified: 07 Dec 2018 11:12
URI: http://oro.open.ac.uk/id/eprint/56772
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