Sphingosine-1-phosphate, a novel TREM2 ligand, promotes microglial phagocytosis to protect against ischemic brain injury.

ABSTRACT: The mechanism of sphingosine-1-phosphate (S1P)-mediated phagocytosis remains unknown. Here, we found that S1P or FTY720 (an analog of S1P) promoted microglial phagocytosis in stroke independent of S1PRs. First, we used computer simulation of molecular docking to predict that S1P might be a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). Next, microscale thermophoresis (MST), surface plasmon resonance (SPR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to reveal that S1P was a novel TREM2 ligand. Then, we confirmed the pro-phagocytosis of S1P targeting in Trem2-Dap12 transfected CHO cells and TREM2 knockdown microglia. Point mutation analysis showed that D104 was the critical binding residue. Trem2 ^-/- mice

SUBMITTER: Xue T 

PROVIDER: S-EPMC9279640 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature