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Nature ; 615(7950): 151-157, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36509106

RESUMEN

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.


Asunto(s)
Colitis , Eosinófilos , Inmunidad , Intestinos , Animales , Humanos , Ratones , Colitis/inmunología , Colitis/patología , Eosinófilos/clasificación , Eosinófilos/citología , Eosinófilos/inmunología , Eosinófilos/metabolismo , Enfermedades Inflamatorias del Intestino/inmunología , Análisis de Expresión Génica de una Sola Célula , Transcriptoma , Proteoma , Interleucina-33 , Interferón gamma , Linfocitos T , Antígeno B7-1/metabolismo , Intestinos/inmunología , Intestinos/patología
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