Comprehensive insights into the roles of eosinophils in the mucosal immunity of gastrointestinal tract: defenders, destructors, and modulators

Eosinophils have long been recognized as terminal effector cells in type 2 immunity; however, emerging evidence positions them as central regulators of intestinal homeostasis, immune modulation, and tissue adaptation. This review provides a comprehensive overview of gastrointestinal eosinophils, integrating recent advances in their development, regulatory mechanisms, functional subsets, and pleiotropic roles across tissues. The developmental and homing pathways that guide eosinophils to the gut are first discussed, with an emphasis on niche-derived signals that control their survival and localization. The functional heterogeneity of intestinal eosinophils is then highlighted, revealing marked transcriptional and spatial diversification. The diverse functions of gut eosinophils are further summarized, including their contributions to pathogen defense, tissue repair, mutual regulation with the microbiota, anti-tumor, and interactions with immune cells. Finally, the cross-tissue orchestration of eosinophil behavior is examined, with a focus on the gut–immune axis. By synthesizing current knowledge, this review aims to present a holistic picture of gastrointestinal eosinophil biology and to inspire new perspectives for understanding and treating eosinophil-associated intestinal disorders.