Characterization of Dendritic Cells Subpopulations in Skin and Afferent Lymph in the Swine Model
Characterization of Dendritic Cells Subpopulations in Skin and Afferent Lymph in the Swine Model
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DOI：
10.1371/journal.pone.0016320
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发表时间：
2011-01-27
期刊：
影响因子：
3.7
通讯作者：
Bertho, Nicolas
中科院分区：
文献类型：
--
作者：
Marquet, Florian;Bonneau, Michel;Bertho, Nicolas
将疫苗经皮递送至特定皮肤树突状细胞（DC）亚群预计是一种有前景的策略，可诱导强烈且特定类型的免疫反应，例如耐受性、细胞毒性或体液免疫。由于人和猪皮肤在组织学上具有惊人的相似性，猪被认为是研究皮肤给药的最合适模型。因此，提高对猪皮肤 DC 亚群的了解对于皮肤疫苗领域非常有价值。在本研究中，我们发现猪皮 DC 包含经典的表皮朗格汉斯细胞 (LC) 和真皮 DC (DDC)，根据其表型可分为 3 个亚群：(1) CD163(neg)/CD172a(neg)、(2) CD163(high)CD172a(pos) 和 (3) CD163(low)CD172a(pos) DDC。这些亚型具有从皮肤迁移到淋巴结的能力，因为我们在假传入淋巴中检测到了它们。使用一组标记进行的广泛表型分析表明，CD163（高）DDC 类似于诱导抗体反应的人皮肤 DC/巨噬细胞，而 CD163（阴性）CD172（低）DDC 与诱导 CD8（+）T 细胞反应的鼠皮肤 CD103（正）DC 具有相同的特性。这项工作通过显示人、小鼠和猪皮肤 DC 之间的相似性，将猪确立为开发针对 DC 的经皮免疫策略的首选模型。
Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC) and dermal DC (DDC) that could be divided in 3 subsets according to their phenotypes: (1) the CD163(neg)/CD172a(neg), (2) the CD163(high)CD172a(pos) and (3) the CD163(low)CD172a(pos) DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163(high) DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163(neg)CD172(low) DDC share properties with the CD8(+) T cell response-inducing murine skin CD103(pos) DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.