Fig. 4

Iluzanebart (ILU) rescues the effects of CSF1R inhibition in human MDM and iPSC microglia. A-B Human Monocyte Derived Macrophages (hMDM). Iluzanebart counteracts the effects of pharmacological CSF1R inhibition on confluence (A) and morphology (B) of MDMs in vitro (n = 3 independent experiments). Treatment of hMDM cells with PLX5622 (iCSF1R) led to a reduction in cell confluence and morphology (striped bars). Treatment with iluzanebart (10 µg/ml; blue bar) restored cellular confluence and ramified morphology, whereas treatment with IgG at the same concentration (green bars) had no effect. C-E iPSC Derived Human Microglia (iMGL). C Treatment with PLX5622 (iCSF1R) decreased iPSC microglia cell viability, as measured by CellTiterGlo (grey bar). Treatment with iluzanebart (75 µg/ml; blue bar) led to a significant restoration of viability, whereas treatment with IgG control at the same concentration (green bar) had no effect (n = 4 independent experiments). D iMGL. Treatment with PLX5622 (iCSF1R) altered iMGL morphology (grey bar). Treatment with iluzanebart (75 µg/ml) restored cellular confluence and ramified morphology (blue bar), whereas treatment with IgG control had no effect (n = 4 independent experiments). E iMGL. Treatment with PLX5622 (iCSF1R) (n = 4 independent experiments) increased numbers of caspase 3/7 positive cells in iPSC microglia cultures (grey bar). Treatment with iluzanebart (75 µg/ml) led to a significant reduction in caspase 3/7 + cells (blue bar), whereas treatment with IgG control had no effect (green bar). Significance was determined by one-way ANOVA with Tukey’s multiple comparison’s test. * < 0.05, ** < 0.05, *** < 0.0005, **** < 0.0001