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Active eosinophils regulate host defense and immune responses in colitis

Abstract

In the past decade, single-cell transcriptomics has helped uncover new cell types and states and led to the construction of a cellular compendium of health and disease1. Still, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils, elusive granulocytes implicated in a plethora of human pathologies2,3, are among these uncharted cell types. To date, the heterogeneity of eosinophils and the gene programs underpinning their pleiotropic functions remain poorly understood4. In the present study, we provide the first comprehensive single-cell transcriptomic profiling of murine eosinophils. We identify an active and a basal population of intestinal eosinophils, differing in their transcriptome, surface proteome and spatial localization. By means of a genome wide CRISPR inhibition screen and functional assays, we dissect a mechanism by which IL-33 and IFN-ɣ induce active eosinophil accumulation 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 inflammatory bowel disease patients and tightly associate with CD4+ T cells. Our findings provide novel insights into the biology of this elusive cell type and highlight its crucial contribution to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
04 Faculty of Medicine > Institute of Experimental Immunology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2 March 2023
Deposited On:04 Jan 2023 08:02
Last Modified:28 Aug 2024 01:39
Publisher:Nature Publishing Group
ISSN:0028-0836
OA Status:Closed
Publisher DOI:https://doi.org/10.1038/s41586-022-05628-7
PubMed ID:36509106
Project Information:
  • Funder: SNF
  • Grant ID: PCEFP3_187021
  • Project Title:
  • Funder: SNF
  • Grant ID: PCEFP3_181249
  • Project Title:
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