The active contribution of OPCs to neuroinflammation is mediated by LRP1
| Autor: | Scott M. Seki, Delaney Liskey, Rebecca M. Beiter, Emily Farber, Megan S Chappell, Christopher C. Overall, David M. Johanson, Suna Onengut-Gumuscu, Jeffrey L. Dupree, Dorian A. Rosen, Anthony Fernandez-Castaneda, Alban Gaultier |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell type Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Cell Culture Techniques Inflammation Biology Neuroprotection Article Pathology and Forensic Medicine Glial scar 03 medical and health sciences Cellular and Molecular Neuroscience Myelin Cuprizone Mice 0302 clinical medicine medicine Animals Humans Neuroinflammation Oligodendrocyte Precursor Cells Multiple sclerosis Histocompatibility Antigens Class I Cell Differentiation medicine.disease LRP1 Mice Inbred C57BL stomatognathic diseases 030104 developmental biology medicine.anatomical_structure nervous system Neurology (clinical) medicine.symptom Neuroscience 030217 neurology & neurosurgery Low Density Lipoprotein Receptor-Related Protein-1 |
| Zdroj: | Acta Neuropathol |
| ISSN: | 1432-0533 |
| Popis: | Oligodendrocyte progenitor cells (OPCs) account for about 5% of total brain and spinal cord cells, giving rise to myelinating oligodendrocytes that provide electrical insulation to neurons of the CNS. OPCs have also recently been shown to regulate inflammatory responses and glial scar formation, suggesting functions that extend beyond myelination. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifaceted phagocytic receptor that is highly expressed in several CNS cell types, including OPCs. Here, we have generated an oligodendroglia-specific knockout of LRP1, which presents with normal myelin development, but is associated with better outcomes in two animal models of demyelination (EAE and cuprizone). At a mechanistic level, LRP1 did not directly affect OPC differentiation into mature oligodendrocytes. Instead, animals lacking LRP1 in OPCs in the demyelinating CNS were characterized by a robust dampening of inflammation. In particular, LRP1-deficient OPCs presented with impaired antigen cross-presentation machinery, suggesting a failure to propagate the inflammatory response and thus promoting faster myelin repair and neuroprotection. Our study places OPCs as major regulators of neuroinflammation in an LRP1-dependent fashion. |
| Databáze: | OpenAIRE |
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