Oncostatin M protects against demyelination by inducing a protective microglial phenotype
Related Experiment Video
Updated: Apr 13, 2026
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Kris Janssens1, Anurag Maheshwari1, Chris Van den Haute2,3
1Department of Immunology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
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.
Insights
Oncostatin M (OSM) protects the central nervous system from demyelination by promoting anti-inflammatory responses. This discovery highlights OSM as a potential therapy for multiple sclerosis and other CNS demyelinating diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic CNS disease causing demyelination and axonal damage, with current therapies unable to halt neurological decline.
- Oncostatin M (OSM), an IL-6 family cytokine, is present in MS lesions and promotes neuronal survival.
- Developing therapies to prevent demyelination and axonal degeneration is a critical unmet need in MS treatment.
Purpose of the Study:
- To investigate the role of Oncostatin M (OSM) and its receptor (OSMR) in demyelination.
- To evaluate the therapeutic potential of OSM in CNS demyelinating diseases.
Main Methods:
- Utilized a cuprizone-induced demyelination model in the central nervous system.
- Examined Oncostatin M receptor (OSMR) expression on microglia/macrophages and astrocytes.
- Assessed the effects of CNS-targeted OSM treatment and OSMR deficiency on demyelination.
- Measured Interleukin-4 (IL-4) expression and myeloid cell polarization in vivo.
Main Results:
- OSMR was significantly upregulated on microglia/macrophages and astrocytes during demyelination.
- OSMR deficiency exacerbated demyelination, while OSM treatment largely prevented it.
- OSM administration increased IL-4 levels and promoted an anti-inflammatory M2 phenotype in myeloid cells.
Conclusions:
- OSM plays a protective role in preventing demyelination in the CNS.
- OSM signaling modulates immune cell responses, shifting them towards an anti-inflammatory state.
- OSM represents a promising therapeutic candidate for treating demyelinating diseases like MS.
