Investigating repopulation of the epidermal Langerhans cell network by distinct progenitor populations

成人组织，如皮肤，在整个生命过程中由细胞维持，这些细胞具有保持分裂和产生该组织特有的新细胞的能力。这些细胞含有控制其分裂能力的基因，但也受到组织中产生的控制细胞发育的因素的影响。然而，通过损伤破坏组织可能会破坏某些细胞群并改变所产生的环境因素。我们感兴趣的是了解新的细胞是如何取代那些因受伤而失去的细胞，并在组织愈合后重新定居。表皮是皮肤的外层，形成一个防水屏障，保护我们免受脱水和感染。皮肤经常暴露于损伤，表皮包含几个不同的细胞群，这些细胞群继续分裂以维持组织。其中，朗格汉斯细胞（LC）是控制皮肤免疫反应的专门细胞群。最初发育（分化）成LC的祖细胞在出生前进入胚胎的皮肤。一旦它们变成LC，它们就有能力继续分裂，并且以这种方式LC数量在皮肤中无限期地保持。然而，如果皮肤受伤，LC被杀死，那么新的祖细胞必须从血液中进入，以取代丢失的细胞。这些细胞与最初进入胚胎皮肤的细胞不同，我们不知道它们分化成的LC是否与原始LC在保持分裂和控制皮肤免疫反应的能力方面相同。我们也不知道什么类型的细胞能够在皮肤损伤后取代受损的LC网络。我们在实验室开发了一种实验模型，其中皮肤中的轻度损伤导致LC被杀死并被新细胞取代，我们可以跟踪。我们的研究旨在利用这个模型来回答三个问题：1。不同祖细胞损伤后皮肤的再增殖如何影响新LC网络维持和控制皮肤免疫反应的能力？2.哪些细胞在受伤后从血液中进入以取代LC？3.表皮中的其他细胞是否产生控制从血液进入的新祖细胞分化的因子？总之，我们从这项研究中获得的数据将帮助我们回答有关LC生物学的基本问题，以及特定于某种细胞类型的因素如何与损伤后组织中的环境因素一起工作，以确保一旦组织愈合，细胞群得到维持。

Adult tissues, such as the skin, are maintained throughout life by cells that have the ability to keep dividing and producing new cells specific to that tissue. These cells contain genes that control their ability to carry on dividing, but are also influenced by factors produced in the tissue that control how the cells develop. However, disruption of the tissue through injury may destroy certain populations of cells and change the environmental factors produced. We are interested in understanding how new cells that replace those lost through injury are programmed to re-colonise the tissue once it has healed.The epidermis is the outer layer of the skin, and forms a water-tight barrier that protects us from dehydration and infection. The skin is constantly exposed to injury, and the epidermis contains several different populations of cells that continue to divide to maintain the tissue. Of these, Langerhans cells (LC) are a specialised population of cells that control immune responses in the skin. The progenitor cells that originally develop (differentiate) into LC enter the skin of the embryo before birth. They have the ability to keep dividing once they become LC, and in this way LC numbers are maintained in the skin indefinitely. If the skin is injured however, and LC are killed, then new progenitor cells must enter from the blood to replace the missing cells. These are different from the cells that originally entered the embryonic skin, and we do not know whether the LC that they differentiate into are the same as the original LC in terms of their ability to keep dividing and to control immune responses in the skin. We also do not know what types of cells are able to replace the damaged LC network after skin injury.We have developed an experimental model in our laboratory, in which mild injury in the skin results in killing of the LC and their replacement by new cells, which we can track. Our research aims to use this model to answer three questions:1. How does the repopulation of the skin after injury by different progenitor cells affect the ability of the new LC network to be maintained and control skin immune responses?2. Which cells enter from the blood to replace LC after injury?3. Do other cells in the epidermis produce factors that control the differentiation of the new progenitors that enter from the blood?Together, the data we get from this research will help us to answer basic questions about the biology of LC, and also about how factors which are specific to a certain cell type work together with environmental factors in the tissue after injury to ensure that the cell population is maintained once the tissue has healed.