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

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-07-09 Epub Date: 2024-05-21 DOI:10.1016/j.immuni.2024.04.027
Joseph Jorssen, Glenn Van Hulst, Kiréna Mollers, Julien Pujol, Georgios Petrellis, Antonio P Baptista, Sjoerd Schetters, Frédéric Baron, Jo Caers, Bart N Lambrecht, Benjamin G Dewals, Fabrice Bureau, Christophe J Desmet
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Abstract

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.

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单细胞蛋白质组学和转录组学捕捉了嗜酸性粒细胞的发育过程,并确定了IL-5在嗜酸性粒细胞系转运放大过程中的作用。
与其他免疫细胞相比,尽管使用了针对嗜酸性粒细胞生成促进细胞因子白细胞介素(IL)-5或其受体IL-5Rα的生物疗法,但嗜酸性粒细胞的活动、本体和系扩增机制仍未得到很好的研究。我们结合单细胞蛋白质组学和转录组学,生成了转基因IL-5Rα报告小鼠,以重新研究嗜酸性粒细胞的生成。我们协调了人类和小鼠的嗜酸性粒细胞生成,并在嗜酸性粒细胞成熟的不同阶段提供了广泛的细胞表面免疫表型和转录组。我们利用这些资源表明,IL-5 通过转运扩增促进了嗜酸性粒细胞系的扩增,而其缺失或中和不会影响嗜酸性粒细胞的成熟。根据我们的资源,我们还发现干扰素反应因子-8(被认为是骨髓造血的重要启动子)并非嗜酸性粒细胞造血所必需。因此,这项工作为了解嗜酸性粒细胞的本体发育、当前精准疗法的效果以及健康和疾病中嗜酸性粒细胞发育和数量的调控提供了资源、方法和见解。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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