AXL-Induced Autophagy mitigates experimental autoimmune encephalomyelitis by suppressing microglial inflammation via the PI3K/AKT/mTOR signaling pathway

Microglia, being the primary immune cells of the central nervous system (CNS), are responsible for pathological inflammatory demyelination in multiple sclerosis (MS). It has been demonstrated that AXL, one of the receptor tyrosine kinases, could alleviate the inflammatory response of microglia. However, the specific mechanism remains unclear. Herein, we explored the role of AXL in the autophagy of microglia and its effect on the experimental autoimmune encephalomyelitis (EAE) model. We revealed that knockout of AXL in BV2 microglia significantly promoted the expression of phosphorylated-PI3K/p-AKT/p-mTOR while significantly inhibiting LC3-Ⅱ/Beclin1. Similarly, autophagy was significantly inhibited in the AXL-/- mice. Knockout of AXL induced serious symptoms, infiltration of inflammatory cells, and demyelination changes, manifesting as the upregulation of pro-inflammatory factors TNF-α and IL-6 and downregulation of anti-inflammatory factors TGF-β and IL-10. In conclusion, this study substantiated that autophagy induced by AXL inhibited the inflammatory response of microglia and alleviated symptoms of EAE. Autophagy activation was mediated by the PI3K/AKT/mTOR signaling pathway.