Immune modulation with poly I:C and recombinant Granulin A enhanced macrophage-dependent debris clearance, increased cardiomyocyte proliferation, and reduced scar burden in medaka hearts.
Immune modulation with poly I:C and Granulin A promotes macrophage-mediated cardiac repair and regeneration in a nonregenerative medaka model.
Myocardial infarction results in irreversible cardiomyocyte loss and fibrotic remodeling in adult mammals, whereas some vertebrates retain the ability to regenerate cardiac tissue. Comparative studies suggest that immune responses critically influence repair outcomes, yet the immune programs associated with regeneration remain incompletely defined. Here, we investigate how immune modulation accelerates cardiac repair in the nonregenerative medaka ( Oryzias latipes ). Using bulk and single-cell transcriptomics combined with functional assays, we show that stimulation with the Toll-like receptor 3 agonist poly I:C accelerates early immune activation and enhances macrophage-dependent debris clearance, associated with inflammatory resolution after cardiac injury. Single-cell analysis of enriched myeloid populations identifies regeneration-associated macrophage subsets characterized by phagocytic and immune-regulatory gene programs, including elevated expression of granulin-a ( grna ). Spatial analysis by hybridization chain reaction reveals increased numbers of grna -expressing macrophages in the injury border zone, coinciding with the regenerative niche of cardiomyocyte proliferation. Consistent with these findings, administration of recombinant Granulin A enhances cardiomyocyte proliferation and reduces scar burden in medaka hearts. Together, these findings indicate that immune modulation reshapes macrophage functional states during cardiac repair and link macrophage-associated granulin expression to regenerative outcomes, highlighting macrophage properties as a potential target for improving heart repair.
Chowdhury et al. (Tue,) conducted a other in Cardiac injury / Myocardial infarction. Toll-like receptor 3 agonist poly I:C and recombinant Granulin A was evaluated on Macrophage-dependent debris clearance, cardiomyocyte proliferation, and scar burden. Immune modulation with poly I:C and recombinant Granulin A enhanced macrophage-dependent debris clearance, increased cardiomyocyte proliferation, and reduced scar burden in medaka hearts.