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.
摘要：
活动,个体发育，嗜酸性粒细胞谱系扩增的机制比其他免疫细胞的机制更不能很好地解决，尽管使用了针对促进嗜酸性粒细胞增多的细胞因子白细胞介素（IL）-5或其受体的生物疗法，IL-5Rα。我们结合了单细胞蛋白质组学和转录组学，并产生了转基因IL-5Rα报告小鼠，以重新审视嗜酸性粒细胞生成。我们调和了人和鼠嗜酸性粒细胞的生成，并在嗜酸性粒细胞成熟的连续过程中的不同阶段提供了广泛的细胞表面免疫表型和转录组。我们使用这些资源来证明IL-5通过转运扩增促进嗜酸性粒细胞谱系扩增，而其缺失或中和不会损害嗜酸性粒细胞的成熟。从我们的资源中得知，我们还表明，干扰素反应因子-8，被认为是骨髓生成的重要启动子，不是嗜酸性粒细胞生成的内在要求。因此，这项工作提供了资源，方法,以及了解嗜酸性粒细胞个体发育的见解，当前精确疗法的效果，以及健康和疾病中嗜酸性粒细胞发育和数量的调节。
