Single-cell proteomics and transcriptomics capture eosinophil development and identify the role of IL-5 in their lineage transit amplification.

Autor: Jorssen J; Laboratory of Cellular and Molecular Immunology, GIGA Institute, Faculty of Veterinary Medicine, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium., Van Hulst G; Laboratory of Cellular and Molecular Immunology, GIGA Institute, Faculty of Veterinary Medicine, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium., Mollers K; Laboratory of Cellular and Molecular Immunology, GIGA Institute, Faculty of Veterinary Medicine, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium., Pujol J; Laboratory of Cellular and Molecular Immunology, GIGA Institute, Faculty of Veterinary Medicine, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium., Petrellis G; Laboratory of Parasitology, FARAH Institute, University of Liege, Faculty of Veterinary Medicine, Avenue de Cureghem 10, 4000 Liege, Belgium., Baptista AP; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Schetters S; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Baron F; Laboratory of Haematology, GIGA Institute, Faculty of Medicine, Liege University Hospital Centre, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium., Caers J; Laboratory of Haematology, GIGA Institute, Faculty of Medicine, Liege University Hospital Centre, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium., Lambrecht BN; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, the Netherlands., Dewals BG; Laboratory of Parasitology, FARAH Institute, University of Liege, Faculty of Veterinary Medicine, Avenue de Cureghem 10, 4000 Liege, Belgium., Bureau F; Laboratory of Cellular and Molecular Immunology, GIGA Institute, Faculty of Veterinary Medicine, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium., Desmet CJ; Laboratory of Cellular and Molecular Immunology, GIGA Institute, Faculty of Veterinary Medicine, University of Liege, B34 Avenue de l'Hopital 1, 4000 Liege, Belgium. Electronic address: christophe.desmet@uliege.be.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2024 Jul 09; Vol. 57 (7), pp. 1549-1566.e8. Date of Electronic Publication: 2024 May 21.
DOI: 10.1016/j.immuni.2024.04.027
Abstrakt: The activities, ontogeny, and mechanisms of lineage expansion of eosinophils are less well resolved than those of other immune cells, despite the use of biological therapies targeting the eosinophilia-promoting cytokine interleukin (IL)-5 or its receptor, IL-5Rα. We combined single-cell proteomics and transcriptomics and generated transgenic IL-5Rα reporter mice to revisit eosinophilopoiesis. We reconciled human and murine eosinophilopoiesis and provided extensive cell-surface immunophenotyping and transcriptomes at different stages along the continuum of eosinophil maturation. We used these resources to show that IL-5 promoted eosinophil-lineage expansion via transit amplification, while its deletion or neutralization did not compromise eosinophil maturation. Informed from our resources, we also showed that interferon response factor-8, considered an essential promoter of myelopoiesis, was not intrinsically required for eosinophilopoiesis. This work hence provides resources, methods, and insights for understanding eosinophil ontogeny, the effects of current precision therapeutics, and the regulation of eosinophil development and numbers in health and disease.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE