166 Chapter 7 Table 2. Immunologic interplay between astrocytes and oligodendrocytes. Detrimental Beneficial Refs Astrocyte mediator Impact on oligodendrocytes TNF-α Induces demyelination and oligodendrocyte necrosis Induces PDGF, and LIF on astrocytes which enhances OPC survival and differentiation 3,95-99 IL-1β Induces oligodendrocyte apoptosis and hypomyelination 100 IFN-γ Reversibly reduces OPC proliferation Limits inflammation, limits Th17 activation, limits IL-1β signalling, protects oligodendrocytes from endoplasmic reticulum stress 101-104 FGF-2 Induces loss of myelin and myelin-producing oligodendrocytes Induces proliferation of OPCs 4,105 BMP BMPs induce OPC differentiation into the astrocyte lineage 24,106 CNTF Induces proliferation and differentiation of OPCs 24,107 IGF-1 Induces OPC differentiation 24,108,109 Oligodendrocyte mediator Impact on astrocytes CCL2 Reduces IL-6 expression in astrocytes, leading to a less inflammatory environment 91,110,111 CXCL10 Induces CXCR3 receptor expression 110,112 IL-17 Induces GFAP, IL-1β, and VEGF, reduces BBB integrity Induces astrogliosis 88,113 IL-1β Induces IL-1β and NF-κB, and P2X7 receptor. 89,91,114,115 GM-CSF Inhibits glial scar formation. Induces proliferation, and migration of astrocytes 92,116 Abbreviations: BMP, bone morphogenic protein, CNTF, ciliary neurotrophic factor; FGF, Fibroblast growth factor; IFN, interferon; IGF, insulin-like growth factor; LIF, Leukaemia inhibitory factor; OPC, oligodendrocyte precursor cell; PDGF, Platelet-derived growth factor; TNF, tumour necrosis factor. stroke, where the glial scar secretes growth inhibiting factors that prevent axonal regrowth127, and in MS, where OPC migration into demyelinated lesions is inhibited25. Astrocytes become reactive in response to both direct and indirect activation; indirect activation is mediated by cytokines secreted by microglia, while direct activation is mediated by damage or pathogen associated molecular patterns that are released by pathogens or during cell death, oxidative stress, or chemical stress3,25. This implies that oligodendrocyte
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