Active eosinophils regulate host defence and immune responses in colitis

0571280 - ÚMG 2024 RIV GB eng J - Článek v odborném periodiku
Gurtner, A. - Borrelli, C. - Gonzalez-Perez, I. - Bach, K. - Acar, I. E. - Nunez, N. G. - Crepaz, D. - Handler, K. - Vu, V. P. - Lafzi, A. - Stirm, K. - Raju, D. - Gschwend, J. - Basler, K. - Schneider, C. - Slack, E. - Valenta, Tomáš - Becher, B. - Krebs, P. - Moor, A. E. - Arnold, I. C.
Active eosinophils regulate host defence and immune responses in colitis.
Nature. Roč. 615, Mar (2023), č. článku 7950. ISSN 0028-0836. E-ISSN 1476-4687
Grant CEP: GA ČR GA21-26025S; GA MŠMT LX22NPO5102
Institucionální podpora: RVO:68378050
Klíčová slova: gene-expression * cells * mice * asthma * CD63 * VIVO * IL-1
Obor OECD: Cell biology
Impakt faktor: 64.8, rok: 2022
Způsob publikování: Open access
https://www.nature.com/articles/s41586-022-05628-7

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 pathologies(1-5)-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-gamma (IFN gamma) 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.
Trvalý link: https://hdl.handle.net/11104/0342542