Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell-macrophage lineage.
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.
Egeler
R Maarten
RM
Department of Pediatric Immunology, Hematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands. rm.egeler@lumc.nl
van Halteren
Astrid G S
AG
Hogendoorn
Pancras C W
PC
Laman
Jon D
JD
Leenen
Pieter J M
PJ
D000818:Animals; D019070:Cell Lineage / Q000276:immunology; D004195:Disease Models, Animal; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology