[Dihydroartemisinin ameliorates inflammation in experimental autoimmune encephalomyelitis by enhancing AXL signaling in microglia].

This study aimed to investigate the mechanism of dihydroartemisinin(DHA) in ameliorating multiple sclerosis(MS). Hematoxylin and eosin(HE) staining was used to assess inflammatory cell infiltration, while luxol fast blue(LFB) staining and electron microscopy were performed to evaluate myelin sheath structure. In cell experiments, this study measured programmed cell death ligand 1(PD-L1) expression on BV2 cells and forkhead box protein p3(Foxp3) expression in Jurkat T cells co-cultured with BV2 cells, determined the C-C motif chemokine ligand 5(CCL5) concentration in the supernatant of BV2 cells, and evaluated BV2 cell chemotaxis. Western blot(WB) was performed to detect protein levels of receptor tyrosine kinase(AXL), phosphorylated AXL(p-AXL), signal transducer and activator of transcription 1(STAT1), phosphorylated STAT1(p-STAT1), and suppressors of cytokine signaling 3(SOCS3). To confirm the role of AXL, key cellular assays were repeated following inhibition of AXL. Additionally, under physiological conditions, the effects of DHA on body weight, spleen weight, and peripheral blood immune cell profiles were examined. The results showed that DHA significantly reduced disease scores, attenuated body weight loss, suppressed inflammatory infiltration, and promoted myelin sheath repair in experimental autoimmune encephalomyelitis(EAE) mice. At the cellular level, DHA upregulated PD-L1 expression on BV2 cells and Foxp3 expression in co-cultured Jurkat cells, and inhibited CCL5 release and BV2 cell chemotaxis. It also upregulated AXL, p-AXL, p-STAT1, and SOCS3 protein expression in BV2 cells. When AXL was inhibited, these effects are nullified. In healthy mice, DHA did not have any effect on their various parameters. In conclusion, DHA maintains inflammatory homeostasis in the EAE model by activating the AXL signaling pathway in microglia.