权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Population structure of myeloid cells in healthy and diseased human lungs.

健康和患病人肺中骨髓细胞的种群结构。

基本信息

批准号：
347286815
负责人：
Professorin Dr. Christine Falk
金额：
--
依托单位：
Institut für Pathologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/347286815?language=en
关键词：
Population structure myeloid cells healthy

项目摘要

The lung is one of three organs that is directly exposed to pathogens and particles from the environment. Not surprisingly, the lung requires a local immune system that allows for fast and effective responses against such pathogens, yet secures organ integrity and function during any insult, infectious or non-infectious. Under homeostatic conditions, the lung harbors specialized immune cells including alveolar macrophages (AM), conventional and plasmacytoid dendritic cells (DCs), mast cells, innate lymphoid cells (ILCs), invariant natural killer T (iNKT) cells, NK cells, memory T cells, and regulatory T cells (Treg). Our understanding of immune cells has been greatly accelerated by classical phenotyping and functional analysis of cell surface marker defined immune cell populations. However, current phenotyping technologies used to distinguish subpopulations have also generated contradictory results. While a significant step forward, even technologies such as CyTof assessing 40 and more parameters are not designed to identify a subpopulation structure of immune cells in an entirely unbiased fashion. Particularly for the myeloid cell compartment in tissues such as the human lung, it is becoming increasingly difficult using classical approaches to unequivocally describe, understand and study the existing cellular heterogeneity and plasticity, not only in homeostasis, but particularly under pathological conditions.We hypothesize that we can gain a higher understanding of the true immune cell population structure of the human lung and the pathophysiology of the major diseases of the lung if we can assess the cellular compartments of the human lungs immune system, particularly the myeloid cell compartment at an unprecedented level of resolution (several hundred genes/per cell). We further hypothesize that such a high-resolution analysis is required to better understand the functionality of pulmonary immune system.With the advent of sequencing technologies on the single cell level (e.g. scRNA-seq), a completely new avenue has been opened and we are now in the position to apply such technologies to describe the true population structure of an organ of interest. Since technologies such as scRNA-seq have never been applied to immune cells in human healthy lung tissue and since we are in the fortunate position to combine our expertise in lung transplant biology, lung immune biology, macrophage biology, scRNA-seq, transcriptomics and bioinformatics, we propose to use scRNA-seq to discover the true population structure in the myeloid cell compartment of the human lung and to define the clinical impact of the new subpopulation structure for lung diseases and transplantation.

肺是直接暴露于环境中病原体和颗粒物的三个器官之一。毫不奇怪，肺部需要一个局部免疫系统，允许对此类病原体做出快速有效的反应，同时确保器官的完整性和功能，无论是传染性的还是非传染性的侮辱。在动态平衡条件下，肺内含有特殊免疫细胞，包括肺泡巨噬细胞(AM)、常规树突状细胞(DC)和浆细胞样树突状细胞(DC)、肥大细胞、固有淋巴样细胞(ILCs)、不变自然杀伤T细胞(INKT)、NK细胞、记忆T细胞和调节性T细胞(Treg)。通过对细胞表面标志物定义的免疫细胞群体的经典表型和功能分析，我们对免疫细胞的理解大大加快了。然而，目前用于区分亚群的表型技术也产生了相互矛盾的结果。虽然这是一项重要的进步，但即使是像CyTof评估40个或更多参数这样的技术，也不是为了以完全公正的方式识别免疫细胞的亚群结构而设计的。尤其是对于人类肺等组织中的髓系细胞，使用经典的方法来明确描述、理解和研究现存的细胞异质性和可塑性变得越来越困难，不仅在稳态下，而且在病理条件下也是如此。我们假设，如果我们能够以前所未有的分辨率(每个细胞数百个基因/细胞)评估人类肺免疫系统的细胞系，特别是髓系细胞系，我们就可以更好地了解人类肺的真实免疫细胞群结构和主要疾病的病理生理学。我们进一步假设，为了更好地了解肺免疫系统的功能，需要这样的高分辨率分析。随着单细胞水平上的测序技术(例如scRNA-seq)的出现，一条全新的途径已经打开，我们现在能够应用这些技术来描述感兴趣器官的真实种群结构。由于scRNA-seq等技术从未被应用于人类健康肺组织中的免疫细胞，而且我们有幸将我们在肺移植生物学、肺免疫生物学、巨噬细胞生物学、scRNA-seq、转录学和生物信息学方面的专业知识结合在一起，我们建议使用scRNA-seq来发现人类肺髓系细胞间的真实种群结构，并确定新的亚群结构对肺部疾病和移植的临床影响。