Revolutionizing mucosal defense: IL-25-educated effector-memory ILC2s redefine innate immune memory

As the primary interface between the host and its environment, the mucosal immune system balances commensal tolerance, nutrient absorption, and pathogen defense. A recent breakthrough by Cortez et al. (2025), published in Cell, identified a novel population of "effector-memory type 2 innate lymphoid cells" (emILC2s). The study shows that IL-25 induces persistent epigenetic reprogramming in ILC2s, establishing robust anti-pathogen defenses across multiple organs and positioning innate cells as key drivers of tissue homeostasis. This work establishes the central role of emILC2s in tissue adaptation, demonstrating their ability to translate transient environmental stimuli into durable, multi-tissue defense and metabolic homeostasis.