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

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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.