Explosive cytotoxicity of ‘ruptoblasts’ bridges hormonal surveillance and immune defense

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 that also acts 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 any 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 mechanisms, the explosive nature of ruptosis relies on intracellular calcium and dynamic cytoskeletal reorganization. Ruptoblast-like cells appear conserved in diverse basal bilaterians, implying an ancient evolutionary origin. These findings unveil a widespread strategy coupling hormonal regulation with immune defense and expand the landscape of evolutionary immune innovations.