英国威康桑格研究所Sarah A. Teichmann研究小组取得一项新突破。他们绘制出了人类肺部的细胞图谱，用于发现健康和哮喘患者中新的细胞状态。 相关论文发表在2019年7月出版的《Nature Medicine》杂志上。

研究组使用单细胞转录组学来绘制健康肺的上下呼吸道和肺实质的细胞结构，以及哮喘肺的下呼吸道。课题组研究了位置依赖型的呼吸道上皮细胞状态和组织驻留记忆T细胞这一新的子集。在哮喘患者的下呼吸道，黏液细胞增生表现为一种新的黏液纤毛细胞状态，以及杯状细胞增生。研究报告了哮喘肺中存在致病性效应2型辅助T细胞(T_H2)，并发现了2型细胞因子维持已发生变化的上皮细胞状态的证据。对细胞与细胞相互作用的无偏分析表明，健康肺的呼吸道结构细胞间通讯在哮喘肺中转变为了以T_H2为主的相互作用。

据介绍，人的肺能够有效地进行气体交换，并与环境形成界面，而环境依赖于粘膜免疫来保护机体免受感染因子的侵袭。结构细胞和免疫细胞之间的相互作用需要严格控制，以维持肺的稳态。

附：英文原文

Title: A cellular census of human lungs identifies novel cell states in health and in asthma

Author: Felipe A. Vieira Braga, Gozde Kar, Marijn Berg, Orestes A. Carpaij, Krzysztof Polanski, Lukas M. Simon, Sharon Brouwer, Toms Gomes, Laura Hesse, Jian Jiang, Eirini S. Fasouli, Mirjana Efremova, Roser Vento-Tormo, Carlos Talavera-Lpez, Marnix R. Jonker, Karen Affleck, Subarna Palit, Paulina M. Strzelecka, Helen V. Firth, Krishnaa T. Mahbubani, Ana Cvejic, Kerstin B. Meyer, Kourosh Saeb-Parsy, Marjan Luinge, Corry-Anke Brandsma, Wim Timens, Ilias Angelidis, Maximilian Strunz, Gerard H. Koppelman, Antoon J. van Oosterhout, Herbert B. Schiller, Fabian J. Theis, Maarten van den Berge, Martijn C. Nawijn, Sarah A. Teichmann

Issue&Volume: Volume 25 Issue 7, July 2019

Abstract: Human lungs enable efficient gas exchange and form an interface with the environment, which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (T_H2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cellcell interactions identifies a shift from airway structural cell communication in healthy lungs to a T_H2-dominated interactome in asthmatic lungs.

DOI: 10.1038/s41591-019-0468-5

Source:https://www.nature.com/articles/s41591-019-0468-5