Active eosinophils regulate host defence and immune responses in colitis

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, Deeksha Raju, Julia Gschwend, Konrad Basler, Christoph Schneider, Emma Slack, Tomas Valenta, Burkhard Becher, Philippe Krebs, Andreas E. Moor () and Isabelle C. Arnold ()
Additional contact information
Alessandra Gurtner: University of Zürich
Costanza Borrelli: ETH Zürich
Ignacio Gonzalez-Perez: University of Zürich
Karsten Bach: ETH Zürich
Ilhan E. Acar: ETH Zürich
Nicolás G. Núñez: University of Zürich
Daniel Crepaz: University of Zürich
Kristina Handler: ETH Zürich
Vivian P. Vu: University of Bern
Atefeh Lafzi: ETH Zürich
Kristin Stirm: University of Zürich
Deeksha Raju: University of Zürich
Julia Gschwend: University of Zürich
Konrad Basler: University of Zürich
Christoph Schneider: University of Zürich
Emma Slack: ETH Zürich
Tomas Valenta: University of Zürich
Burkhard Becher: University of Zürich
Philippe Krebs: University of Bern
Andreas E. Moor: ETH Zürich
Isabelle C. Arnold: University of Zürich

Nature, 2023, vol. 615, issue 7950, 151-157

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41586-022-05628-7

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