Extended Data Fig. 2: ST2 genetic ablation inhibits the induction of the chemotactic transcriptomic state in microglia after interleukin-33 treatment.

a, Bar plot showing the distance between chemotactic microglia (that is, Vcam1⁺ Cx3cr1⁺ cells) and the nearest amyloid-beta (Aβ) plaque 3, 8, and 24 h after interleukin-33 (IL-33) treatment (n = 4 mice per condition; one-way ANOVA with Dunnett’s multiple comparisons test). b, Venn diagram showing the overlap between 529 differentially expressed genes (DEGs) (IL-33–treated APP;ST2KO vs. IL-33-treated APP;ST2WT mice) and the signature genes of chemotactic microglia (n = 4 per condition). c, Bar plots showing the expression levels of the representative chemotactic signature genes in the 3 conditions (Wald test from DESeq2). d-f, Genetic ablation of ST2 in microglia inhibits the Aβ chemotaxis of microglia and microglia-mediated Aβ clearance upon IL-33 treatment. d, Schematic diagram showing the protocol for tamoxifen and IL-33 administration in APP/PS1;ST2-icKO mice. e,f, Bar plots showing the proportions of Aβ plaque-associated microglia (e) and Aβ levels in cortical regions (f) after IL-33 treatment in APP/PS1;ST2-icKO mice (wild-type [WT] Con: n = 5; WT IL-33: n = 6; icKO Con: n = 6; icKO IL-33: n = 6; two-way ANOVA with Šidák’s multiple comparisons test). g-i, The induction of VCAM1⁺ chemotactic microglia is a generalized IL-33 response in microglia. g, Bar plot showing the expression level of Vcam1 in microglia 3 h after IL-33 treatment (WT Con: n = 4; WT IL-33: n = 5; APP/PS1 Con: n = 3; APP/PS1 IL-33: n = 3; two-way ANOVA with Šidák’s multiple comparisons test). h,i, Representative images (h) and quantification (i) showing the proportion of chemotactic microglia (that is, Vcam1⁺ Cx3cr1⁺ cells) after interleukin-33 (IL-33) treatment in WT mice (n = 3 mice per condition; two-tailed unpaired Student’s t-test). Arrowheads indicate Vcam1-expressing microglia. Scale bar = 10 μm. All data are mean ± s.e.m.

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