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TAM receptors regulate multiple features of microglial physiology

2016; Nature Portfolio; Volume: 532; Issue: 7598 Linguagem: Inglês

10.1038/nature17630

1476-4687

Lawrence Fourgeaud, Paqui G. Través, Yusuf Tufail, Humberto Leal‐Bailey, Erin D. Lew, Patrick Burrola, Perri C. Callaway, Anna Zagórska, Carla V. Rothlin, Axel Nimmerjahn, Greg Lemke,

Adenosine and Purinergic Signaling

Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl 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 is normally driven by both TAM receptor ligands Gas6 and protein S. 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. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.