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Fig. 2 Iluzanebart is a specific agonist of human TREM2. A hTREM1-HEK. In a HEK293T cell line expressing hTREM1 and hDAP12, an <t>anti-TREM1</t> antibody (green) stimulated phosphorylation of SYK after 45-min treatment, whereas iluzanebart (blue) did not (n = 3 independent experiments), confirming that iluzanebart is a TREM2-specific agonist with no cross-reactivity to the related TREM1 receptor. B TREM2 -/- iMGL. Iluzanebart (blue) does not stimulate pSYK in TREM2−/− human iPSC-derived microglia. Concanavalin A (green) was used as a positive control demonstrating that TREM2−/− cells can activate pSYK in response to TREM2-independent activators. Data shown is normalized to IgG control after 5 min exposure (n = 2 independent experiments) and reported as % of maximal activation. C iPSC Derived Human iMGL. Treatment of human iPSC microglia with iluzanebart reduced levels of soluble TREM2 levels after 24 h, compared to IgG control which had no effect (n = 2 independent experiments)
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Fig. 2 Iluzanebart is a specific agonist of human TREM2. A hTREM1-HEK. In a HEK293T cell line expressing hTREM1 and hDAP12, an anti-TREM1 antibody (green) stimulated phosphorylation of SYK after 45-min treatment, whereas iluzanebart (blue) did not (n = 3 independent experiments), confirming that iluzanebart is a TREM2-specific agonist with no cross-reactivity to the related TREM1 receptor. B TREM2 -/- iMGL. Iluzanebart (blue) does not stimulate pSYK in TREM2−/− human iPSC-derived microglia. Concanavalin A (green) was used as a positive control demonstrating that TREM2−/− cells can activate pSYK in response to TREM2-independent activators. Data shown is normalized to IgG control after 5 min exposure (n = 2 independent experiments) and reported as % of maximal activation. C iPSC Derived Human iMGL. Treatment of human iPSC microglia with iluzanebart reduced levels of soluble TREM2 levels after 24 h, compared to IgG control which had no effect (n = 2 independent experiments)

Journal: Journal of neuroinflammation

Article Title: Rescue of in vitro models of CSF1R-related adult-onset leukodystrophy by iluzanebart: mechanisms and therapeutic implications of TREM2 agonism.

doi: 10.1186/s12974-025-03346-1

Figure Lengend Snippet: Fig. 2 Iluzanebart is a specific agonist of human TREM2. A hTREM1-HEK. In a HEK293T cell line expressing hTREM1 and hDAP12, an anti-TREM1 antibody (green) stimulated phosphorylation of SYK after 45-min treatment, whereas iluzanebart (blue) did not (n = 3 independent experiments), confirming that iluzanebart is a TREM2-specific agonist with no cross-reactivity to the related TREM1 receptor. B TREM2 -/- iMGL. Iluzanebart (blue) does not stimulate pSYK in TREM2−/− human iPSC-derived microglia. Concanavalin A (green) was used as a positive control demonstrating that TREM2−/− cells can activate pSYK in response to TREM2-independent activators. Data shown is normalized to IgG control after 5 min exposure (n = 2 independent experiments) and reported as % of maximal activation. C iPSC Derived Human iMGL. Treatment of human iPSC microglia with iluzanebart reduced levels of soluble TREM2 levels after 24 h, compared to IgG control which had no effect (n = 2 independent experiments)

Article Snippet: R&D anti-mouse/anti-rat antibody (#MAB17291), R&D Systems] anti-human TREM1 antibody (#MAB1278), Concanavalin A (Sigma, #C2010), PLX5622 (MedChem Express, #50-196-9292), IL4 (Peprotech #200-04).

Techniques: Expressing, Phospho-proteomics, Derivative Assay, Positive Control, Control, Activation Assay