Langerhans Cell Histiocytosis
Langerhans Cell Histiocytosis (LCH) is the most common of the rare group of disorders that constitute histiocytosis, with an approximate incidence of three to seven cases per million, predominantly but not exclusively in children. This disorder affects all age groups, but the features are better defined in children than in adults. The current paradigm suggests that LCH results from an accumulation of epidermal dendritic cells (DCs) also known as Langerhans cells (LCs). This concept is based on phenotypical and ultrastuctural observations showing that LCH lesions are infiltrated by CD1a+ and langerin+ cells, two features thought to be restricted to epidermal LCs. It has been difficult to understand how LCs, which are normally restricted to stratified epithelia, could give rise to such a multi-focal disorder.
Recent data from our group suggests that LCH is not a disease of epidermal LCs, but instead derives from the accumulation of blood-derived interstitial langerin+ DCs. Based on our research, we hypothesize that LCH is due to an accumulation of interstitial langerin+ DCs, and not LCs, and can be characterized by dysregulated molecular pathways in the former. One of our primary goals is therefore to understand the mechanisms that lead to langerin+ DC accumulation in LCH lesions and identify novel therapeutic targets that should lead to the treatment of this condition.