Fig. 9

MSD analysis of iluzanebart-treated mouse cortical tissue reveals dose-dependent, TREM2-dependent changes in cytokine levels. A-C hTREM2-CV mice (n = 4–6 mice per group) were treated with iluzanebart (IP; 1, 3, 10, 30, 100, or 200 mg/kg), IgG (100 mg/kg), or saline. Cortical tissue was harvested 24 h after treatment. Levels of the cytokine IP10 (A), MIP1α (B), and MCP1 (C) showed a dose–response effect in response to iluzanebart treatment, whereas IgG-treated had no change in levels in any of these factors compared to saline-treated controls. D Cytokine levels measured by MSD in cortical tissue from hTREM2^+/+ mice or hTREM2.^−/− mice, perfused and collected 24 h after intraperitoneal dose of 200 mg/kg iluzanebart. Three chemokines expected to respond to TREM2 agonism demonstrated a significant increase relative to vehicle after 24 h, while no significant increase in these chemokines was observed in mice lacking TREM2. IL15, a cytokine not expected to respond to TREM2 agonism, was included as a negative control. Data shown is reported as % of vehicle control. Significance was determined by one-way ANOVA with Dunnett’s multiple comparison’s test, * < 0.05, ** < 0.05, *** < 0.0005, **** < 0.0001