RRC ID 34769
Author Janssens K, Maheshwari A, Van den Haute C, Baekelandt V, Stinissen P, Hendriks JJ, Slaets H, Hellings N.
Title Oncostatin M protects against demyelination by inducing a protective microglial phenotype.
Journal Glia
Abstract Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS), in which destruction of myelin sheaths leads to disturbed axonal conduction. Available MS therapies modulate the immune response, but are unable to prevent neurological decline. Therefore, great efforts are made to develop therapies that limit demyelination and axonal degeneration. Oncostatin M (OSM), a member of the interleukin (IL)-6 cytokine family, is produced in demyelinating lesions of MS patients and stimulates neuronal survival. In this study, we reveal that the OSM receptor (OSMR) was robustly upregulated on microglia/macrophages and astrocytes in the cuprizone-induced demyelination model. While OSMR deficiency led to aggravated demyelination, CNS-targeted OSM treatment largely prevented demyelination. OSM treatment increased IL-4 expression and induced polarization of myeloid cells towards an anti-inflammatory M2 phenotype in vivo. This study reveals a previously uncharacterized and protective role for OSM during demyelination, and indicates that OSM is a promising therapeutic candidate to limit CNS damage in demyelinating diseases including MS.
Volume 63(10)
Pages 1729-37
Published 2015-10-1
DOI 10.1002/glia.22840
PMID 25921393
MeSH Animals Calcium-Binding Proteins / metabolism Central Nervous System / drug effects Central Nervous System / metabolism Central Nervous System / pathology Chelating Agents / toxicity Cuprizone / toxicity Cytokines / genetics Cytokines / metabolism Demyelinating Diseases / chemically induced Demyelinating Diseases / pathology* Demyelinating Diseases / prevention & control* Disease Models, Animal Glial Fibrillary Acidic Protein / metabolism Growth Inhibitors / pharmacology Male Mice Mice, Inbred C57BL Mice, Knockout Microfilament Proteins / metabolism Microglia / drug effects Microglia / metabolism* Oncostatin M / pharmacology* Oncostatin M Receptor beta Subunit / genetics Oncostatin M Receptor beta Subunit / metabolism Phenotype Time Factors Transduction, Genetic Up-Regulation / drug effects Up-Regulation / genetics Up-Regulation / physiology*
IF 5.984
Times Cited 10
Mice RBRC02711