Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands.
Front Immunol. 2019 Aug 14;10:1932. doi: 10.3389/fimmu.2019.01932. eCollection 2019.
The human fetal immune system must protect the infant against the sudden exposure to a large variety of pathogens upon birth. While it is known that the fetal immune system develops in sequential waves, relatively little is known about the composition of the innate and adaptive immune system in the tissues. Here, we applied high-dimensional mass cytometry to profile the immune system in human fetal liver, spleen, and intestine. With Hierarchical Stochastic Neighbor Embedding (HSNE) we distinguished 177 distinct immune cell clusters, including both previously identified and novel cell clusters. PCA analysis indicated substantial differences between the compositions of the immune system in the different organs. Through dual t-SNE we identified tissue-specific cell clusters, which were found both in the innate and adaptive compartment. To determine the spatial location of tissue-specific subsets we developed a 31-antibody panel to reveal both the immune compartment and surrounding stromal elements through analysis of snap-frozen tissue samples with imaging mass cytometry. Imaging mass cytometry reconstructed the tissue architecture and allowed both the characterization and determination of the location of the various immune cell clusters within the tissue context. Moreover, it further underpinned the distinctness of the immune system in the tissues. Thus, our results provide evidence for early compartmentalization of the adaptive and innate immune compartment in fetal spleen, liver, and intestine. Together, our data provide a unique and comprehensive overview of the composition and organization of the human fetal immune system in several tissues.
人类胎儿的免疫系统必须在出生时保护婴儿免受大量病原体的突然侵袭。虽然人们知道胎儿的免疫系统是按顺序发展的，但对于组织中先天和适应性免疫系统的组成，人们知之甚少。在这里，我们应用高维质谱流式细胞术来描绘人胎儿肝脏、脾脏和肠道中的免疫系统。通过层次随机邻嵌入（HSNE），我们区分了 177 个独特的免疫细胞簇，包括先前已鉴定和新的细胞簇。主成分分析（PCA）表明不同器官的免疫系统组成存在显著差异。通过双 t-SNE 我们鉴定了组织特异性的细胞簇，这些细胞簇存在于先天和适应性免疫区室中。为了确定组织特异性亚群的空间位置，我们开发了一个 31 抗体面板，通过对冰冻组织样本进行成像质谱流式细胞术分析，揭示免疫区室和周围基质成分。成像质谱流式细胞术重建了组织架构，允许对各种免疫细胞簇在组织背景中的特征和位置进行鉴定。此外，它进一步支持了组织中免疫系统的独特性。因此，我们的结果为胎儿脾脏、肝脏和肠道中适应性和先天免疫区室的早期分区提供了证据。总之，我们的数据提供了人类胎儿在几个组织中免疫系统组成和组织的独特而全面的概述。
