Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.
Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.
复制标题
人类气道巨噬细胞和树突状细胞子集的转录分类和功能表征。
DOI：
10.4049/jimmunol.1600777
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发表时间：
2017-02-01
期刊：
影响因子：
--
通讯作者：
Metcalf JP
中科院分区：
文献类型：
--
作者：
Patel VI;Booth JL;Duggan ES;Cate S;White VL;Hutchings D;Kovats S;Burian DM;Dozmorov M;Metcalf JP
The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Due to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole lung bronchoalveolar lavage. Six subsets of phagocytic antigen presenting (HLA-DR+) cells were consistently observed. Aside from alveolar macrophages, subsets of Langerin+, BDCA1− CD14+, BDCA1+ CD14+, BDCA1+ CD14−, and BDCA1− CD14− cells were identified. These subsets varied in their ability to internalize Escherichia coli, Staphylococcus aureus, and Bacillus anthracis particles. All subsets were more efficient at internalizing S. aureus and B. anthracis compared to E. coli. Alveolar macrophages and CD14+ cells were overall more efficient at particle internalization compared to the four other populations. Subsets were further separated into two groups based on their inherent capacities to upregulate surface CD83, CD86, and CCR7 expression levels. Whole genome transcriptional profiling revealed a clade of “true dendritic cells” consisting of Langerin+, BDCA1+ CD14+, and BDCA1+ CD14− cells. The dendritic cell clade was distinct from a macrophage/monocyte clade, as supported by higher mRNA expression levels of several dendritic cell-associated genes, including CD1, FLT3, CX3CR1, and CCR6. Each clade, and each member of both clades, were discerned by specific upregulated genes, which can serve as markers for future studies in healthy and diseased states.
