Fig. 8

SIRPα modulates microglial efferocytosis and neuroinflammation following experimental SAH via the SHP1/STAT6 axis. SAH induces extensive neuronal cell death, resulting in the release of DAMPs. These DAMPs, along with hemoglobin and cellular corpses, trigger localized inflammation. SIRPα inhibits efferocytosis by recruiting and phosphorylating SHP1 and SHP2 through the phosphorylation of four tyrosine residues in its cytoplasmic domain, with SHP1 playing a particularly critical role. Mutation of these tyrosine residues to alanine enhances efferocytosis and reduces neuroinflammation both in vivo and in vitro, through dephosphorylation of p-STAT6 and subsequent upregulation of the transcription of Mertk and Cd36