Active eosinophils regulate host defence and immune responses in colitis

Area of Science:

• Immunology
• Cell Biology
• Genomics

Background:

• Single-cell transcriptomics has advanced cell atlases but misses some cell types.
• Eosinophils, granulocytes involved in many diseases, remain poorly understood due to their heterogeneity.
• Understanding eosinophil function is crucial for human health and disease.

Purpose of the Study:

• To comprehensively profile mouse eosinophils using single-cell transcriptomics.
• To identify distinct eosinophil populations and their underlying gene programs.
• To elucidate the mechanisms regulating eosinophil activation and function in the gut.

Main Methods:

• Single-cell RNA sequencing of mouse intestinal eosinophils.
• Genome-wide CRISPR inhibition screening.
• Functional assays and proteomic analysis.
• Spatial localization studies.

Main Results:

• Identified two distinct intestinal eosinophil populations: active and basal.
• Discovered that interleukin-33 (IL-33) and interferon-γ (IFNγ) induce active eosinophils in inflamed colons.
• Active eosinophils exhibit bactericidal and T cell regulatory functions, expressing CD80 and PD-L1.
• Found active eosinophils enriched in inflammatory bowel disease patients, associated with CD4+ T cells.

Conclusions:

• Eosinophils are crucial for intestinal homeostasis, immune regulation, and host defense.
• Characterized a mechanism for eosinophil activation in gut inflammation.
• Provides a framework for studying eosinophils in human gastrointestinal diseases.