Wells Steven B, Rainbow Daniel B, Mark Michal, Szabo Peter A, Ergen Can, Caron Daniel P, Maceiras Ana Raquel, Rahmani Elior, Benuck Eli, Valiollah Pour Amiri Valeh, Chen David, Wagner Allon, Howlett Sarah K, Jarvis Lorna B, Ellis Karen L, Kubota Masaru, Matsumoto Rei, Mahbubani Krishnaa, Saeb-Parsy Kouresh, Conde Cecilia Dominguez, Richardson Laura, Xu Chuan, Li Shuang, Mamanova Lira, Bolt Liam, Wilk Alicja, Teichmann Sarah A, Farber Donna L, Sims Peter A, Jones Joanne L, Yosef Nir
Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
Nat Immunol. 2025 Aug 13. doi: 10.1038/s41590-025-02241-4.
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.
免疫系统由多种细胞谱系和亚群组成，这些细胞谱系和亚群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中超过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、固有淋巴细胞和髓细胞）及其相应亚群进行注释，以便在不同组织部位和年龄之间进行比较。我们确定了对各谱系免疫细胞组成和功能的主要位点特异性影响；年龄相关影响在粘膜部位的巨噬细胞、淋巴器官中的B细胞以及血液和组织中的循环T细胞和自然杀伤细胞中，因位点和谱系而异。我们的结果揭示了全身免疫稳态的组织特异性特征，据此可定义人类整个生命周期中的免疫病理学。
