Klechevsky Eynav
Washington University School of Medicine, St. Louis, USA,
Adv Exp Med Biol. 2015;850:43-54. doi: 10.1007/978-3-319-15774-0_4.
At the crossroad between innate and adaptive immunity are the dendritic Cells (DCs), a "novel cell type." discovered in 1973 by Ralph Steinman. Although not entirely appreciated at first, it is clear that they play a critical role as specialized antigen-presenting cells and essential mediators in shaping immune reactivity and tolerance. Dendritic cells are now recognized as a heterogeneous group of cells in terms of cell-surface markers, anatomic location, and function adapted to protect against an array of pathogens and conditions. Importantly, these subsets are also unique to each species. While significant progress has been made on the identification and function of mouse DC subsets, much less is known about human cells. Here we review the fascinating biology of human skin DCs and describe tolerogenic principles that are critical in maintaining immune homeostasis and for controlling inflammation, as well as mechanisms that are fundamental to confer immunity. We surmise that these principles could be applied to DCs across organs, and could be harnessed for the treatment of various human autoimmune, inflammatory diseases, as well as cancer. Importantly, to leverage the relevance of basic research to the clinical setting, it is first necessary to determine the functional homology between mouse and human DCs. We discuss practical steps towards this aim.
处于固有免疫和适应性免疫交叉点的是树突状细胞（DCs），这是一种1973年由拉尔夫·斯坦曼发现的“新型细胞类型”。尽管一开始并未得到充分认识，但很明显，它们作为特殊的抗原呈递细胞和塑造免疫反应性及耐受性的重要介质发挥着关键作用。就细胞表面标志物、解剖位置以及适应抵御一系列病原体和病症的功能而言，树突状细胞现在被认为是一组异质性细胞。重要的是，这些亚群在每个物种中也都是独特的。虽然在小鼠DC亚群的鉴定和功能方面已经取得了重大进展，但对人类细胞的了解却少得多。在这里，我们综述了人类皮肤DCs迷人的生物学特性，并描述了在维持免疫稳态和控制炎症方面至关重要的致耐受性原理，以及赋予免疫能力的基本机制。我们推测这些原理可应用于全身各器官的DCs，并可用于治疗各种人类自身免疫性、炎症性疾病以及癌症。重要的是，为了利用基础研究与临床应用的相关性，首先有必要确定小鼠和人类DCs之间的功能同源性。我们讨论了实现这一目标的实际步骤。
