小柯机器人

瑞士苏黎世大学Isabelle C. Arnold等研究人员合作发现，活跃的嗜酸性粒细胞调节结肠炎的宿主防御和免疫反应。2022年12月12日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员提供了第一个全面的小鼠嗜酸性粒细胞的单细胞转录组分析。研究人员确定了一个活跃的和一个基础的肠道嗜酸性粒细胞群体，它们的转录组、表面蛋白组和空间定位都不同。通过全基因组CRISPR抑制筛选和功能试验，研究人员剖析了IL-33和IFN-?在炎症结肠中诱导活跃嗜酸性粒细胞聚集的机制。活跃的嗜酸性粒细胞具有杀菌和T细胞调节活性，并表达共刺激分子CD80和PD-L1。值得注意的是，活跃的嗜酸性粒细胞在一小部分炎症性肠病患者的固有层中富集，并与CD4⁺T细胞紧密结合。这项发现为这种难以捉摸的细胞类型的生物学提供了新的见解，并强调其对肠道平衡、免疫调节和宿主防御的关键贡献。此外，研究人员为人类胃肠道疾病中嗜酸性粒细胞的特征奠定了一个框架。

据介绍，在过去十年中，单细胞转录组学已经帮助发现了新的细胞类型和状态，并导致了健康和疾病的细胞图谱的构建。然而，一些难以排序的细胞仍然没有出现在组织图谱中。嗜酸性粒细胞是一种难以捉摸的粒细胞，与大量的人类病症有牵连，是这些未知的细胞类型之一。迄今为止，对嗜酸性粒细胞的异质性和支撑其多种功能的基因程序仍然知之甚少。

附：英文原文

Title: Active eosinophils regulate host defense and immune responses in colitis

Author: Gurtner, Alessandra, Borrelli, Costanza, Gonzalez-Perez, Ignacio, Bach, Karsten, Acar, Ilhan E., Nez, Nicols G., Crepaz, Daniel, Handler, Kristina, Vu, Vivian P., Lafzi, Atefeh, Stirm, Kristin, Raju, Deeksha, Gschwend, Julia, Basler, Konrad, Schneider, Christoph, Slack, Emma, Valenta, Tomas, Becher, Burkhard, Krebs, Philippe, Moor, Andreas E., Arnold, Isabelle C.

Issue&Volume: 2022-12-12

Abstract: In the past decade, single-cell transcriptomics has helped uncover new cell types and states and led to the construction of a cellular compendium of health and disease1. Still, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils, elusive granulocytes implicated in a plethora of human pathologies2,3, are among these uncharted cell types. To date, the heterogeneity of eosinophils and the gene programs underpinning their pleiotropic functions remain poorly understood4. In the present study, we provide the first comprehensive single-cell transcriptomic profiling of murine eosinophils. We identify an active and a basal population of intestinal eosinophils, differing in their transcriptome, surface proteome and spatial localization. By means of a genome wide CRISPR inhibition screen and functional assays, we dissect a mechanism by which IL-33 and IFN- induce active eosinophil accumulation 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 inflammatory bowel disease patients and tightly associate with CD4+ T cells. Our findings provide novel insights into the biology of this elusive cell type and highlight its crucial contribution to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.

DOI: 10.1038/s41586-022-05628-7

Source: https://www.nature.com/articles/s41586-022-05628-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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