Extended Data Fig. 9: rIL-3 delivery to the cortex or periphery of 5xFAD mice and summary figure.

a, Recombinant IL-3 or PBS was delivered into the cortex of 5xFAD mice. Three days later, localization of microglia to Aβ aggregates was assessed (n = 7 PBS mice; n = 6 rIL-3 mice). Two-tailed Mann–Whitney U-tests. b, Scheme of rIL-3 delivery intraperitoneally twice a week for 10 weeks to 5xFAD mice. c, Prior to death, Y-maze behavioural testing was performed and time in the new arm was quantified (n = 7 PBS mice; n = 8 rIL-3 mice). d, The amount of Aβ in the cortex of mice was quantified by analysing histological sections (n = 6). Groups of mice are of evenly mixed sex. **P < 0.01. Mean ± s.e.m. e, Model of the role of IL-3 in AD. Astrocytes produce IL-3. In response to Aβ, TREM2 signalling increases microglia IL-3Rα, rendering microglia responsive to astrocyte-derived IL-3. IL-3 signalling instigates transcriptional and functional programming of microglia, which leads to a signature of immune regulation, motility, and migration. IL-3-dependent programming promotes clustering of microglia around Aβ, which enables clearance of Aβ and mitigation of AD pathology.