Lagumersindez-Denis, Nielsen and Wrzos, Claudia and Mack, Matthias and Winkler, Anne and van der Meer, Franziska and Reinert, Marie C. and Hollasch, Heiko and Flach, Anne and Bruehl, Hilke and Cullen, Eilish and Schlumbohm, Christina and Fuchs, Eberhard and Linington, Christopher and Barrantes-Freer, Alonso and Metz, Imke and Wegner, Christiane and Liebetanz, David and Prinz, Marco and Brueck, Wolfgang and Stadelmann, Christine and Nessler, Stefan (2017) Differential contribution of immune effector mechanisms to cortical demyelination in multiple sclerosis. ACTA NEUROPATHOLOGICA, 134 (1). pp. 15-34. ISSN 0001-6322, 1432-0533
Full text not available from this repository. (Request a copy)Abstract
Cortical demyelination is a widely recognized hallmark of multiple sclerosis (MS) and correlate of disease progression and cognitive decline. The pathomechanisms initiating and driving gray matter damage are only incompletely understood. Here, we determined the infiltrating leukocyte subpopulations in 26 cortical demyelinated lesions of biopsied MS patients and assessed their contribution to cortical lesion formation in a newly developed mouse model. We find that conformation-specific anti-myelin antibodies contribute to cortical demyelination even in the absence of the classical complement pathway. T cells and natural killer cells are relevant for intracortical type 2 but dispensable for subpial type 3 lesions, whereas CCR2(+) monocytes are required for both. Depleting CCR2(+) monocytes in marmoset monkeys with experimental autoimmune encephalomyelitis using a novel humanized CCR2 targeting antibody translates into significantly less cortical demyelination and disease severity. We conclude that biologics depleting CCR2(+) monocytes might be attractive candidates for preventing cortical lesion formation and ameliorating disease progression in MS.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRANSGENIC MICE; MOUSE MODEL; MENINGEAL INFLAMMATION; LESIONS; COMPLEMENT; REMYELINATION; PATHOLOGY; DISEASE; Progressive multiple sclerosis; Cortical demyelination; Experimental autoimmune encephalomyelitis; Inflammatory monocytes |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 18 Feb 2019 15:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1624 |
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