Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

IF 27.6 1区 医学 Q1 IMMUNOLOGY
Steven B. Wells, Daniel B. Rainbow, Michal Mark, Peter A. Szabo, Can Ergen, Daniel P. Caron, Ana Raquel Maceiras, Elior Rahmani, Eli Benuck, Valeh Valiollah Pour Amiri, David Chen, Allon Wagner, Sarah K. Howlett, Lorna B. Jarvis, Karen L. Ellis, Masaru Kubota, Rei Matsumoto, Krishnaa Mahbubani, Kouresh Saeb-Parsy, Cecilia Dominguez Conde, Laura Richardson, Chuan Xu, Shuang Li, Lira Mamanova, Liam Bolt, Alicja Wilk, Sarah A. Teichmann, Donna L. Farber, Peter A. Sims, Joanne L. Jones, Nir Yosef
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Abstract

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20–75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across tissue sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages; age-associated effects were manifested by site and lineage for macrophages in mucosal sites, B cells in lymphoid organs, and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan. Wells et al. profile RNA and surface protein expression to describe dominant tissue-specific effects on immune cell composition and function across lineages in the human tissues across age.

Abstract Image

Abstract Image

多模态分析揭示了人类免疫细胞随年龄变化的组织定向特征
免疫系统由多个细胞系和亚群组成,在整个生命周期中维持在组织中,组织和年龄对免疫细胞功能的影响尚不清楚。在这里,我们全面分析了来自24名年龄在20-75岁的器官捐献者的血液、淋巴组织和粘膜组织的125万个免疫细胞的RNA和表面蛋白表达。我们使用多模态分类器和概率模型对主要谱系(T细胞、B细胞、先天淋巴样细胞和骨髓细胞)和相应的亚群进行注释,以便跨组织部位和年龄进行比较。我们确定了在整个谱系中对免疫细胞组成和功能的显性位点特异性影响;年龄相关的影响表现在粘膜部位的巨噬细胞、淋巴器官的B细胞、血液和组织中的循环T细胞和自然杀伤细胞的位置和谱系上。我们的研究结果揭示了整个身体免疫稳态的组织特异性特征,从中定义了整个人类生命周期的免疫病理。
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来源期刊
Nature Immunology
Nature Immunology 医学-免疫学
CiteScore
40.00
自引率
2.30%
发文量
248
审稿时长
4-8 weeks
期刊介绍: Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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