Strobl H, Riedl E, Bello-Fernandez C, Knapp W
Institute of Immunology, University of Vienna, Austria.
Immunobiology. 1998 Mar;198(5):588-605. doi: 10.1016/S0171-2985(98)80080-6.
Epidermal Langerhans cells (LC) play a critical role in host defense. Still we know rather little about the development and functional specialization of these bone marrow-derived dendritic cells (DC) located in the most peripheral ectodermal tissue of the mammalian organism. How LC develop from their primitive progenitors in bone marrow and to what extent LC are related in their development to other lineages of the hemopoietic system is still under debate. There are currently 3 major areas of debate: 1) which are the signals required for LC development and differentiation to occur, 2) what are the (molecular) characteristics of the intermediate stages of LC differentiation, and 3) how are LC related in their development and/or function to other cells of the hemopoietic system? A better understanding of LC development and answers to these questions can be expected from recently developed technologies which allow the in vitro generation of DC with the typical molecular, morphological and functional features of LC from purified CD34+ progenitor cells under defined serum-free culture conditions. TGF-beta 1 was found to be an absolute requirement for in vitro LC development under serum-free conditions upon stimulation with the classical DC growth and differentiation factors GM-CSF, TNF-alpha and SCF. The recently identified cytokine FLT3 ligand further dramatically enhanced in vitro LC development and even allowed efficient in vitro generation of LC colonies from serum-free single cell cultures of CD34+ hemopoietic progenitor cells.
表皮朗格汉斯细胞（LC）在宿主防御中发挥着关键作用。然而，对于这些位于哺乳动物机体最外周外胚层组织中的骨髓来源的树突状细胞（DC）的发育和功能特化，我们了解得还相当少。LC如何从骨髓中的原始祖细胞发育而来，以及LC在发育过程中与造血系统的其他谱系有多大程度的关联，仍存在争议。目前有3个主要争议领域：1）LC发育和分化发生所需的信号是什么，2）LC分化中间阶段的（分子）特征是什么，3）LC在发育和/或功能上与造血系统的其他细胞有何关联？从最近开发的技术中有望更好地理解LC发育并回答这些问题，这些技术允许在特定的无血清培养条件下，从纯化的CD34 +祖细胞体外生成具有LC典型分子、形态和功能特征的DC。在无血清条件下，用经典的DC生长和分化因子GM-CSF、TNF-α和SCF刺激时，发现TGF-β1是体外LC发育的绝对必要条件。最近鉴定出的细胞因子FLT3配体进一步显著增强了体外LC发育，甚至允许从CD34 +造血祖细胞的无血清单细胞培养物中高效体外生成LC集落。
