小柯机器人

英国威康桑格研究所Gavin J. Wright、Jarrod Shilts等研究人员合作绘制出人类免疫系统的物理联系图。这一研究成果于2022年8月3日在线发表在国际学术期刊《自然》上。

利用高通量表面受体筛选方法，研究人员系统地绘制了一个重组库的直接蛋白质相互作用图谱，该库包括了人类白细胞上可检测到的大多数表面蛋白质。研究人员独立验证并确定了每个新相互作用的生物物理参数，从而对连接人类免疫细胞的受体线路形成了一个高置信度和定量的观点。通过整合这些相互作用组和表达数据，研究人员确定了免疫相互作用的动态趋势，并构建了一个简化的数学模型，从基本原理上预测了细胞的连接。研究人员还开发了一个互动的多组织单细胞图谱，推断出整个身体的免疫相互作用，揭示了新的相互作用的潜在功能背景和多细胞网络的枢纽。最后，研究人员将人类白细胞的靶向蛋白刺激与多重高内涵显微镜结合起来，在调节免疫反应和维持细胞间联系的正常模式方面，将受体互动与功能作用联系起来。总之，这项工作为人类免疫系统的细胞间连接提供了一个系统的视角，从免疫细胞连接的系统级原则延伸到单个受体的机械特性，这可能为治疗性干预提供机会。

据了解，人类免疫系统是由分布在全身的细胞网络组成的，它们必须动态地形成物理联系，并利用其细胞表面蛋白组之间的相互作用进行交流。尽管它们具有治疗潜力，但人们对这些表面相互作用的图谱仍不完整。

附：英文原文

Title: A physical wiring diagram for the human immune system

Author: Shilts, Jarrod, Severin, Yannik, Galaway, Francis, Mller-Sienerth, Nicole, Chong, Zheng-Shan, Pritchard, Sophie, Teichmann, Sarah, Vento-Tormo, Roser, Snijder, Berend, Wright, Gavin J.

Issue&Volume: 2022-08-03

Abstract: The human immune system is composed of a distributed network of cells circulating throughout the body, which must dynamically form physical associations and communicate using interactions between their cell-surface proteomes1. Despite their therapeutic potential2, our map of these surface interactions remains incomplete3,4. Here, using a high-throughput surface receptor screening method, we systematically mapped the direct protein interactions across a recombinant library that encompasses most of the surface proteins that are detectable on human leukocytes. We independently validated and determined the biophysical parameters of each novel interaction, resulting in a high-confidence and quantitative view of the receptor wiring that connects human immune cells. By integrating our interactome with expression data, we identified trends in the dynamics of immune interactions and constructed a reductionist mathematical model that predicts cellular connectivity from basic principles. We also developed an interactive multi-tissue single-cell atlas that infers immune interactions throughout the body, revealing potential functional contexts for new interactions and hubs in multicellular networks. Finally, we combined targeted protein stimulation of human leukocytes with multiplex high-content microscopy to link our receptor interactions to functional roles, in terms of both modulating immune responses and maintaining normal patterns of intercellular associations. Together, our work provides a systematic perspective on the intercellular wiring of the human immune system that extends from systems-level principles of immune cell connectivity down to mechanistic characterization of individual receptors, which could offer opportunities for therapeutic intervention.

DOI: 10.1038/s41586-022-05028-x

Source: https://www.nature.com/articles/s41586-022-05028-x

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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