TAM receptors regulate multiple features of microglial physiology
Microglial phagocytosis is required for neurogenic niche maintenance and response to injury; the TAM kinases Mer and Axl are expressed by microglia in the adult CNS, and mediate the clearance of apoptotic cells from the niche. Mer and Axl regulate microglial physiology Microglial phagocytosis is req...
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Veröffentlicht in: | Nature (London) 2016-04, Vol.532 (7598), p.240-244 |
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Zusammenfassung: | Microglial phagocytosis is required for neurogenic niche maintenance and response to injury; the TAM kinases Mer and Axl are expressed by microglia in the adult CNS, and mediate the clearance of apoptotic cells from the niche.
Mer and Axl regulate microglial physiology
Microglial phagocytosis is required for neurogenic niche maintenance and response to central nervous system (CNS) injury. Here Greg Lemke and colleagues show that the TAM receptor kinases Mer and Axl are expressed by microglia and in the adult CNS, and mediate the clearance of apoptotic cells from the neurogenic niche. This work demonstrates that TAM receptors act as controllers of microglial physiology, and are potential targets for therapeutic intervention in CNS disease.
Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells
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. Here we show that the TAM receptor tyrosine kinases Mer and Axl
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regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis
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,
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is normally driven by both TAM receptor ligands Gas6 and protein S
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. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson’s disease
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. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease. |
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ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/nature17630 |