ILC2-derived α-CGRP promotes angiogenic sprouting and functional recovery though CGRP receptor on endothelial cells. (A) We employed dual AAV-BR1 vectors, with one vector carrying the hICAM2 promoter and SpCas9, and the other containing dual gRNAs targeting Ramp1. The mixed viruses were administered via femoral vein injection in mice, followed by a 21-day expression period prior to subsequent experiments (created with https://BioRender.com). (B) After 21 days of dual viral expression, MCAO was induced. Tissues were collected 5 days after MCAO for immunofluorescence staining. (C) EGFP expression after 21 days of dual viral expression. Scale bar, 100 µm. (D and E) Immunofluorescence and quantification of RAMP1 expression and its vascular coverage in cerebral blood vessels, analyzed by two-sided, unpaired Student’s t test. Data are from biological replicates and represent two independent experiments. ****P < 0.0001. Scale bars, 100 µm. (F) Morphometric quantification of angiogenic sprouting and by calculating the number of tip cells and endothelial cells with filopodia per 40× view, analyzed by two-sided, unpaired Student’s t test. Data are from biological replicates and represent two independent experiments. P > 0.05. (G) Behavioral tests of dual viral-transfected MCAO mice after PBS treatment and ILC2s transfer, analyzed by two-way ANOVA repeated measurement. Data are shown as line charts with error bars (SEM, median). P > 0.05.