CD200 restrains macrophage attack on oligodendrocyte precursors via toll-like receptor 4 downregulation
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CitationHayakawa, Kazuhide, Loc-Duyen D Pham, Ji Hae Seo, Nobukazu Miyamoto, Takakuni Maki, Yasukazu Terasaki, Sava Sakadzic, et al. 2016. “CD200 Restrains Macrophage Attack on Oligodendrocyte Precursors via Toll-Like Receptor 4 Downregulation.” Journal of Cerebral Blood Flow & Metabolism 36 (4) (April): 781–793. doi:10.1177/0271678x15606148.
AbstractThere are numerous barriers to white matter repair after CNS injury and the underlying mechanisms remain to be
fully understood. In this study, we propose the hypothesis that inflammatory macrophages in damaged white
matter attack oligodendrocyte precursor cells (OPCs) via TLR4 signaling thus interfering with this endogenous
progenitor recovery mechanism. Primary cell culture experiments demonstrate that peritoneal macrophages can
attack and digest OPCs via TLR4 signaling, and this phagocytosis of OPCs can be inhibited by using CD200-Fc to downregulate TLR4. In an in vivo model of white matter ischemia induced by endothelin-1, treatment with D200-Fc suppressed TLR4 expression in peripherally circulating macrophages, thus restraining macrophage phagocytosis of OPCs and leading to improved myelination. Taken together, these findings suggest that deleterious macrophage effects may occur after white matter ischemia, whereby macrophages attack OPCs and interfere with endogenous recovery responses. Targeting this pathway with CD200 may offer a novel therapeutic approach to amplify endogenous OPC-mediated repair of white matter damage in mammalian brain.
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