IL7R depletion mitigates neuroinflammation and ischemic stroke via AKT dephosphorylation dependent LCP1 suppression in mice

macrophage subset with high fatty-acid metabolism scores 3 days after ischemic stroke in mice. In vitro oxygen glucose deprivation cell model, Il7r expression was significantly increased, accompanied by upregulation of the PI3K-AKT pathway. IL7R knockdown decreased phosphorylated Akt and LCP1 levels, and LCP1 knockdown further reduced arachidonic acid, a key mediator of pro-inflammatory protein translation, as revealed by bulk RNA-seq and metabolomics analyses. Consistent with these in vitro results, IL7R depleted mice exhibited smaller infarct volumes and improved neurological function. Collectively, our findings provide mechanistic insight into how IL7R-pAKT-LCP1 signaling shapes immune-cell metabolism during stroke-induced neuroinflammation and suggest potential therapeutic opportunities targeting immunometabolic pathways in ischemic stroke.