IFN-γ coordinates macrophage-mediated inflammatory resolution and matrix remodeling in heart regeneration.

In zebrafish heart regeneration, loss of ifng1 disrupts macrophage-driven debris clearance and collagen remodeling, delaying scar resolution and reducing cardiomyocyte protrusion and proliferation.

• Why it matters: Regenerating myocardium depends on immune programs that both resolve inflammation and remodel extracellular matrix, but how IFN-γ shapes macrophage functions during repair is unclear.
• What they did: The study used zebrafish with ifng1 loss, analyzed cardiac macrophage transcriptomes, applied macrophage-specific IFN-γ signaling blockade, and performed nanoparticle-mediated timp4.3 silencing in injured adult hearts and FACS-isolated cardiac macrophages.
• The result: IFN-γ signaling loss caused dysregulated inflammatory and ECM-remodeling programs, including reduced matrix metalloproteinases and increased timp4.3; timp4.3 silencing lowered its expression, improved collagen remodeling and CM protrusion, and partially rescued CM proliferation and scar resolution in ifng1 mutants.

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