In its rare occurrence, Langerhans cell histiocytosis (LCH) is a dangerous but intriguing deviation of mononuclear phagocytes, especially dendritic cells (DCs). Clinically, the disease ranges from self-resolving or well manageable to severe and even fatal. LCH lesions in skin, bone, and other sites contain high numbers of cells with phenotypic features resembling LCs admixed with macrophages, T cells, eosinophils, and multinucleated giant cells. Here we review current progress in the LCH field based on two central questions: (i) are LCH cells intrinsically aberrant, and (ii) how does the lesion drive pathogenesis? We argue that LCH cells may originate from different sources, including epidermal LCs, tissue Langerin+ DCs, or mononuclear phagocyte precursors. Current and prospective in vitro and in vivo models are discussed. Finally, we discuss recent insights into plasticity of T-helper cell subsets in light of the lesion microenvironment. LCH continues to provide urgent clinical questions thereby inspiring innovative DC lineage research.

Cell proliferation, Dendritic cells, Monocytes/macrophages, T lymphocyte, add on therapy, apoptosis, cell cycle regulation, cell lineage, cell maturation, cladribine, clinical trial, corticosteroid, cytarabine, dendritic cell, eosinophil, helper cell, histiocytosis X, human, in vitro study, macrophage, mercaptopurine, natalizumab, priority journal, review, stem cell transplantation, tacrolimus, unspecified side effect, vinblastine,
Immunological Reviews
Erasmus MC: University Medical Center Rotterdam

Egeler, R.M, van Halteren, A.G.S, Hoogendoorn, P.C.W, Laman, J.D, & Leenen, P.J.M. (2010). Langerhans cell histiocytosis: Fascinating dynamics of the dendritic cell-macrophage lineage. Immunological Reviews (Vol. 234, pp. 213–232). doi:10.1111/j.0105-2896.2009.00883.x