Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment
Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment
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DOI：
10.1126/sciimmunol.aai7677
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发表时间：
2016-12-01
影响因子：
24.8
通讯作者：
Dudziak, Diana
中科院分区：
文献类型：
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作者：
Heidkamp, Gordon F.;Sander, Jil;Dudziak, Diana
在小鼠中，常规和浆细胞样树突状细胞(DC)在迁移到周围组织之前来自不同的造血祖细胞。此外，两类常规DC(cDC1和cDC2 DC)和一类浆细胞样DC(PDC)在转录和功能上是不同的实体。在人类中，这三种DC亚型可以使用细胞表面标记CD1c(CDC2)、CD141(CDc1)和CD303(PDCs)来识别，尽管DC的功能是否主要由个体发育或组织微环境决定仍然是难以捉摸的。通过对这三种DC亚型在来自大量人类个体的不同人类组织中的表型和转录谱分析，我们证明了淋巴造血系统器官(脾、胸腺和血液)中的DC亚群强烈地由个体发育而不是由微环境的信号决定。相比之下，来自人肺或皮肤的DC亚群有很大的不同，强烈地认为DC对来自组织微环境的调制信号做出反应。总而言之，这项研究中获得的数据可能成为指导进一步研究动态平衡和炎症期间人类DC生物学的主要资源。
In mice, conventional and plasmacytoid dendritic cells (DCs) derive from separate hematopoietic precursors before they migrate to peripheral tissues. Moreover, two classes of conventional DCs (cDC1 and cDC2 DCs) and one class of plasmacytoid DCs (pDCs) have been shown to be transcriptionally and functionally distinct entities. In humans, these three DC subtypes can be identified using the cell surface markers CD1c (cDC2), CD141 (cDC1), and CD303 (pDCs), albeit it remains elusive whether DC functionality is mainly determined by ontogeny or the tissue microenvironment. By phenotypic and transcriptional profiling of these three DC subtypes in different human tissues derived from a large number of human individuals, we demonstrate that DC subpopulations in organs of the lymphohematopoietic system (spleen, thymus, and blood) are strongly defined by ontogeny rather than by signals from the microenvironment. In contrast, DC subsets derived from human lung or skin differed substantially, strongly arguing that DCs react toward modulatory signals from tissue microenvironments. Collectively, the data obtained in this study may serve as a major resource to guide further studies into human DC biology during homeostasis and inflammation.