Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities
Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities
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DOI：
10.4049/jimmunol.1303150
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发表时间：
2014-12-15
影响因子：
4.4
通讯作者：
Bertho, Nicolas
中科院分区：
文献类型：
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作者：
Marquet, Florian;Manh, Thien-Phong Vu;Bertho, Nicolas
猪皮肤是人体皮肤的最佳结构模型之一，广泛用于探测药物经皮通道和测试新的皮肤接种装置。然而，关于其在免疫细胞中的组成知之甚少，其中树突状细胞（DC）在免疫应答的启动中是必不可少的。在描述了猪皮肤中四种不同DC亚群的第一项开创性工作之后，我们在下文中深化了这些细胞的表征，显示了猪DC亚群与其人类对应物之间的相似性。通过比较转录组学研究、经典表型分析以及体内和体外功能研究，我们发现猪CD163（pos）真皮DC（DDC）与人CD14（pos）DDC在转录组学上相似。CD163（pos）DDC在发炎的皮肤中募集，它们在发炎的淋巴中迁移，但它们不被CCL21吸引，并且它们适度地激活同种异体CD8 T细胞。我们还表明，CD163（低）DDC是转录相似的人CD1a（正）DDC。CD163（低）DDC向CCL21迁移，它们激活同种异体CD8和CD4 T细胞，并且像它们潜在的人肺对应物一样，它们使CD4 T细胞向Th17分布倾斜。因此，我们得出结论，猪皮是一个相关的模型，为人类皮肤接种。
Swine skin is one of the best structural models for human skin, widely used to probe drug transcutaneous passage and to test new skin vaccination devices. However, little is known about its composition in immune cells, and among them dendritic cells (DC), that are essential in the initiation of the immune response. After a first seminal work describing four different DC subpopulations in pig skin, we hereafter deepen the characterization of these cells, showing the similarities between swine DC subsets and their human counterparts. Using comparative transcriptomic study, classical phenotyping as well as in vivo and in vitro functional studies, we show that swine CD163(pos) dermal DC (DDC) are transcriptomically similar to the human CD14(pos) DDC. CD163(pos) DDC are recruited in inflamed skin, they migrate in inflamed lymph but they are not attracted toward CCL21, and they modestly activate allogeneic CD8 T cells. We also show that CD163(low) DDC are transcriptomically similar to the human CD1a(pos) DDC. CD163(low) DDC migrate toward CCL21, they activate allogeneic CD8 and CD4 T cells and, like their potential human lung counterpart, they skew CD4 T cells toward a Th17 profile. We thus conclude that swine skin is a relevant model for human skin vaccination.