Gut eosinophils emerge as central regulators of intestinal homeostasis and immunity

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Frontiers in Medicine Published June 7, 2026 Medically reviewed June 7, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider gastrointestinal eosinophils as central regulators of intestinal homeostasis and immune modulation, not just allergic effectors.

This narrative review examines the evolving understanding of gastrointestinal eosinophils, traditionally viewed as effector cells in allergic inflammation, but now recognized as key players in intestinal homeostasis and immunity. The authors synthesize evidence showing that gut eosinophils exhibit marked transcriptional and spatial diversification, with niche-derived signals controlling their survival and localization. Emerging evidence positions them as central regulators of intestinal homeostasis, immune modulation, and tissue adaptation. The review covers their contributions to pathogen defense, tissue repair, mutual regulation with the microbiota, anti-tumor immunity, and interactions with other immune cells, with a focus on the gut–immune axis. The authors note that while the field is advancing, many aspects remain to be clarified, and the evidence is still emerging. The review aims to inspire new perspectives for understanding and treating eosinophil-associated intestinal disorders, but caution is warranted given the narrative nature of the synthesis and the lack of quantitative pooled data.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

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.