Transcriptional fingerprints of antigen-presenting cell subsets in the human vaginal mucosa and skin reflect tissue-specific immune microenvironments

Transcriptional fingerprints of antigen-presenting cell subsets in the human vaginal mucosa and skin reflect tissue-specific immune microenvironments
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DOI:
10.1186/s13073-014-0098-y
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发表时间:
2014-11-25
期刊:
影响因子:
12.3
通讯作者:
Oh, SangKon
Oh, SangKon
中科院分区:
生物学1区
文献类型:
--
作者:
Duluc, Dorothee;Banchereau, Romain;Oh, SangKon

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背景:树突状细胞分布于全身各处,它们可以感知和捕获入侵的病原体,从而诱导保护性免疫。因此,利用组织树突状细胞的生物学特性是合理设计抗病原体疫苗的基础。方法:本研究利用基因芯片从转录和网络水平分析了人阴道4种抗原提呈细胞亚群(朗格汉斯细胞,CD14(-)和CD14(+)树突状细胞,巨噬细胞)的转录本,并与3种皮肤树突状细胞亚群和血液髓系树突状细胞的基因指纹图谱进行了比较。尽管如此,来自阴道和皮肤的CD14(+)细胞群体倾向于先天免疫和促炎反应,而CD14(-)群体,特别是皮肤和阴道朗格汉斯细胞,以及阴道CD14(-)树突状细胞,既表现出Th2诱导表型,又表现出调节表型。我们还确定了新的阴道抗原提呈细胞亚群的表型和功能生物标志物。结论:我们提供了一个包含人体阴道、皮肤和血液中8个抗原提呈细胞群的87个微阵列样本的转录数据库。总之,这些数据提供了分子信息,将进一步有助于描述人类组织抗原提呈细胞系及其功能。这项研究的数据可以指导性传播病原体的粘膜疫苗的设计。
Background: Dendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity. Hence, harnessing the biology of tissue-resident dendritic cells is fundamental for the rational design of vaccines against pathogens.Methods: Herein, we characterized the transcriptomes of four antigen-presenting cell subsets from the human vagina (Langerhans cells, CD14(-) and CD14(+) dendritic cells, macrophages) by microarray, at both the transcript and network level, and compared them to those of three skin dendritic cell subsets and blood myeloid dendritic cells.Results: We found that genomic fingerprints of antigen-presenting cells are significantly influenced by the tissue of origin as well as by individual subsets. Nonetheless, CD14(+) populations from both vagina and skin are geared towards innate immunity and pro-inflammatory responses, whereas CD14(-) populations, particularly skin and vaginal Langerhans cells, and vaginal CD14(-) dendritic cells, display both Th2-inducing and regulatory phenotypes. We also identified new phenotypic and functional biomarkers of vaginal antigen-presenting cell subsets.Conclusions: We provide a transcriptional database of 87 microarray samples spanning eight antigen-presenting cell populations in the human vagina, skin and blood. Altogether, these data provide molecular information that will further help characterize human tissue antigen-presenting cell lineages and their functions. Data from this study can guide the design of mucosal vaccines against sexually transmitted pathogens.