Author
Abstract
In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils—elusive granulocytes that are implicated in a plethora of human pathologies1–5—are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPR inhibition screen and functional assays, we reveal a mechanism by which interleukin-33 (IL-33) and interferon-γ (IFNγ) induce the accumulation of active eosinophils in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of patients with inflammatory bowel disease, and are closely associated with CD4+ T cells. Our findings provide insights into the biology of eosinophils and highlight the crucial contribution of this cell type to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
Suggested Citation
Alessandra Gurtner & Costanza Borrelli & Ignacio Gonzalez-Perez & Karsten Bach & Ilhan E. Acar & Nicolás G. Núñez & Daniel Crepaz & Kristina Handler & Vivian P. Vu & Atefeh Lafzi & Kristin Stirm & Dee, 2023.
"Active eosinophils regulate host defence and immune responses in colitis,"
Nature, Nature, vol. 615(7950), pages 151-157, March.
Handle:
RePEc:nat:nature:v:615:y:2023:i:7950:d:10.1038_s41586-022-05628-7
DOI: 10.1038/s41586-022-05628-7
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