Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8049 Zürich, Switzerland.
Blood Transfusion Service Zürich, SRC, 8952 Schlieren, Switzerland.
Sci Adv. 2022 Nov 4;8(44):eabn5631. doi: 10.1126/sciadv.abn5631. Epub 2022 Nov 2.
Phenotypic plasticity is essential to the immune system, yet the factors that shape it are not fully understood. Here, we comprehensively analyze immune cell phenotypes including morphology across human cohorts by single-round multiplexed immunofluorescence, automated microscopy, and deep learning. Using the uncertainty of convolutional neural networks to cluster the phenotypes of eight distinct immune cell subsets, we find that the resulting maps are influenced by donor age, gender, and blood pressure, revealing distinct polarization and activation-associated phenotypes across immune cell classes. We further associate T cell morphology to transcriptional state based on their joint donor variability and validate an inflammation-associated polarized T cell morphology and an age-associated loss of mitochondria in CD4 T cells. Together, we show that immune cell phenotypes reflect both molecular and personal health information, opening new perspectives into the deep immune phenotyping of individual people in health and disease.
表型可塑性对于免疫系统至关重要,但塑造它的因素尚未完全了解。在这里,我们通过单轮多重免疫荧光、自动化显微镜和深度学习,全面分析了人类群体的免疫细胞表型,包括形态。利用卷积神经网络的不确定性对八种不同免疫细胞亚群的表型进行聚类,我们发现,由此产生的图谱受供体年龄、性别和血压的影响,揭示了不同免疫细胞类群的极化和激活相关表型。我们进一步根据它们的联合供体变异性将 T 细胞形态与转录状态相关联,并验证了与炎症相关的极化 T 细胞形态和 CD4 T 细胞中与年龄相关的线粒体丧失。总之,我们表明,免疫细胞表型反映了分子和个人健康信息,为深入了解健康和疾病个体的免疫表型提供了新的视角。