Dysregulation of Dendritic Cell Development in Langerhans Cell Histiocytosis
Matthew Collin, MD
Newcastle University – Newcastle upon Tyne, United Kingdom
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Langerhans cell histiocytosis is caused by an abnormal type of dendritic cell known as the LCH cell. About two-thirds of patients have a mutation in BRAF, a gene that controls the development and survival of cells. The major question that we now need to solve is how BRAF makes the dendritic cell become an abnormal LCH cell. We have three experimental aims to attempt to solve this: 1) to find out which of several different types of dendritic cells and other related cells contain the most mutated BRAF in patients with LCH; 2) to study how mutated BRAF affects the generation of dendritic cells from blood stem cells in vitro in the laboratory; 3) to determine what external factors, released from LCH lesions, cooperate with mutated BRAF in pushing dendritic cells to become abnormal LCH cells. We are well placed to tackle these questions because our laboratory is experienced in studying the formation of normal human dendritic cells. It will therefore be possible for us to discern what is abnormal in LCH, using these approaches.