The science and medicine of human immunology.
The science and medicine of human immunology.
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DOI：
10.1126/science.aay4014
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发表时间：
2020-09-25
期刊：
影响因子：
--
通讯作者：
Davis MM
中科院分区：
文献类型：
--
作者：
Pulendran B;Davis MM
哺乳动物的免疫系统是一个显著的感觉系统，用于检测和中和病原体。历史充满了瘟疫的破坏性影响，而2019年冠状病毒病（COVID-19）大流行是我们这个时代的一场决定性全球健康危机。虽然有效疫苗的开发挽救了许多生命，但免疫系统的基本工作是复杂的，需要开发动物模型，如近交系小鼠。事实上，对小鼠的研究已经取得了巨大的成果，收集到的巨大见解导致了许多诺贝尔奖和其他荣誉。然而，过去的结果并不一定是未来的可靠指南，动物模型的一个显着局限性是它们未能准确模拟某些人类疾病，并且在许多情况下无法预测人类免疫反应。关于近交系小鼠，这一直是免疫学的主要模型选择，这可能是由于必要的妥协，以创造一个更听话和可重复的实验系统，如遗传均匀性和缺乏病原体暴露，以及事实上，小鼠是进化上相当独特的。这些考虑表明，从科学和医学的角度来看，对人类免疫系统的直接研究可能是非常有益的。在过去的十年里，有一个爆炸性的新方法和技术，以前所未有的精度探索人类免疫系统。人类对疫苗接种、癌症和病毒感染（如COVID-19）的免疫反应的见解来自高通量“组学”技术，该技术测量基因、mRNA（单细胞转录组学）、蛋白质（蛋白质组学）、代谢物（代谢组学）、细胞（质谱细胞术）和表观遗传修饰（ATAC-seq）的行为，并结合计算方法。悉尼·布伦纳在2008年说：“我们不必再寻找模式生物了。因为我们是模式生物。”我们建议，研究人类的免疫系统，谁是遗传多样性和多种疾病的折磨，提供了一个直接的联系，以医学（即，“翻译”）和非常真实的前景发现从根本上新的人类生物学。新的方法和技术使这一领域变得更加容易，但人类免疫分析只是第一步。在动物模型或人类类器官中进行数据的计算挖掘和生物验证是必不可少的下一步，在一个迭代周期中，该周期旨在将基础科学和应用科学以及小鼠和人类免疫学联系起来，实现科学发现和转化医学的无缝连续。这将代表加速疫苗和治疗剂开发的新范例。探索人类对病毒感染的免疫反应。系统生物学技术可用于探测人类对病毒感染的免疫反应，并可定义预测疾病严重程度和阐明疾病潜在机制的分子特征。虽然有效疫苗的开发已经从传染病中挽救了无数生命，但人类免疫系统的基本工作是复杂的，需要开发动物模型，如近交系小鼠，以确定免疫机制。最近，新的策略和技术已经开发出来，以前所未有的精度直接探索人类免疫系统。我们讨论这些方法是如何推进我们对人类免疫学的机械理解，并促进感染，自身免疫性疾病和癌症的疫苗和治疗方法的发展。
The mammalian immune system is a remarkable sensory system for the detection and neutralization of pathogens. History is replete with the devastating effects of plagues, and the coronavirus disease 2019 (COVID-19) pandemic is a defining global health crisis of our time. Although the development of effective vaccines has saved many lives, the basic workings of the immune system are complex and require the development of animal models, such as inbred mice. Indeed, research in mice has been enormously productive, and the tremendous insights gleaned have resulted in many Nobel prizes and other accolades. However, past results are not necessarily a reliable guide to the future, and a notable limitation of animal models has been their failure to accurately model some human diseases and their inability to predict human immune responses in many cases. With regard to inbred mice, which have been the principal model of choice for immunology, this is likely due to the compromises that were necessary to create a more tractable and reproducible system for experimentation, such as genetic uniformity and lack of pathogen exposure, as well as the fact that mice are evolutionarily quite distinct. These considerations suggest that direct studies of the human immune system are likely to be extremely rewarding, both from a scientific and a medical perspective. In the past decade there has been an explosion of new approaches and technologies to explore the human immune system with unprecedented precision. Insights into the human immune response to vaccination, cancers, and viral infections such as COVID-19 have come from high-throughput “omics” technologies that measure the behavior of genes, mRNA (single-cell transcriptomics), proteins (proteomics), metabolites (metabolomics), cells (mass cytometry), and epigenetic modifications (ATAC-seq), coupled with computational approaches. Sydney Brenner remarked in 2008, “We don’t have to look for a model organism anymore. Because we are the model organisms.” We propose that studying the immune system in humans, who are genetically diverse and afflicted by a multitude of diseases, offers both a direct link to medicine (i.e., “translation”) and the very real prospect of discovering fundamentally new human biology. New approaches and technology are now making this area much more approachable, but profiling immunity in humans is but the first step. Computational mining of the data and biological validation in animal models or human organoids are essential next steps, in an iterative cycle that seeks to bridge fundamental and applied science, as well as mouse and human immunology, in a seamless continuum of scientific discovery and translational medicine. This will represent a new paradigm for accelerating the development of vaccines and therapeutics. Probing the human immune response to viral infections. Systems biology techniques can be used to probe the human immune response to viral infections and can define molecular signatures that predict disease severity and illuminate the underlying mechanisms of disease. Although the development of effective vaccines has saved countless lives from infectious diseases, the basic workings of the human immune system are complex and have required the development of animal models, such as inbred mice, to define mechanisms of immunity. More recently, new strategies and technologies have been developed to directly explore the human immune system with unprecedented precision. We discuss how these approaches are advancing our mechanistic understanding of human immunology and are facilitating the development of vaccines and therapeutics for infection, autoimmune diseases, and cancer.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Brodin P;Jojic V;Gao T;Bhattacharya S;Angel CJ;Furman D;Shen-Orr S;Dekker CL;Swan GE;Butte AJ;Maecker HT;Davis MM
通讯作者：
Davis MM
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
30.5
作者：
Davis MM;Tato CM;Furman D
通讯作者：
Furman D
系统方法用于人类自身免疫性疾病。
影响因子：
7
作者：
Banchereau R;Cepika AM;Pascual V
通讯作者：
Pascual V