Explosive cytotoxicity of ruptoblasts bridges hormone surveillance and immune defense.

Abstract

Current understanding of cytotoxic immunity is shaped by hematopoietic-derived cells-T cells, natural killer cells, and neutrophils. Here, we identify "ruptoblasts," a previously unknown cytotoxic glandular cell type in regenerative planarian flatworms. Ruptoblasts undergo an explosive cell death, "ruptosis," triggered by activin, a multifunctional hormone acting as an inflammatory cytokine. Excessive activin-induced through protein injection, genetic chimerism, or bacterial infection-initiates ruptosis, discharging potent diffusible cytotoxic agents capable of eliminating nearby cells, bacteria, and even mammalian cells within minutes. Ruptoblast ablation suppresses inflammation but compromises bacterial clearance, highlighting their broad-spectrum immune functions. Mechanistically distinct from known cytotoxic and cell death mechanisms, the explosive nature of ruptosis relies on endoplasmic reticulum (ER)-derived calcium and cytoskeleton-dependent signal amplification. Ruptoblast-like cells appear conserved in diverse basal bilaterians, implying an ancient evolutionary origin. These findings unveil a strategy coupling hormonal regulation with immune defense and expand the landscape of evolutionary immune innovations.