The multifaceted ILC3s: Key regulator of mucosal defense and homeostasis

Summary Mucosal tissues serve as a critical interface between the host and the external environment. The mucosal immune system is confronted with the dual challenge of defending against pathogenic threats while maintaining immune tolerance to harmless antigens. Group 3 innate lymphoid cells (ILC3s), which predominantly reside at mucosal barriers, represent essential cornerstones of the body's frontline defense and function as key sentinels and orchestrators of mucosal immunity. Upon sensing signals within the mucosal microenvironment, ILC3s mount rapid responses by producing an array of cytokines, such as IL-22, and cooperate with epithelial cells and other immune cells to preserve host protection and tissue homeostasis. This review highlights the mechanisms by which murine ILC3s orchestrate immune defense against diverse pathogens, explores their contributions to sustaining mucosal integrity, and dissects their crosstalk with the adaptive immune system to maintain immune tolerance, thereby highlighting the central role of ILC3s in mucosal immunity.