Langerhans cell histiocytosis: Fascinating dynamics of the dendritic cell-macrophage lineage

Department of Pediatric Immunology, Hematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Immunological Reviews (Impact Factor: 10.12). 03/2010; 234(1):213-32. DOI: 10.1111/j.0105-2896.2009.00883.x
Source: PubMed


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.

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    • "Langerhans cells are DCs within the epidermis and other squamous epithelia, which rely on M-CSF for their development [60, 62]. In histiocytosis X, the expansion of Langerhans cells is manifested by either granuloma formation or a more diffuse proliferative disease [63]. "
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    • "LCH is a rare disease in which the lesional cells resemble LC. It has been hypothesized that the putative cells in LCH may arise from epidermal LC, dermal and lymphoid tissue resident dendritic cells or mononuclear phagocyte precursors.[6] LCH is composed of three morphologically similar lesions: Hand-Schuller-Christian syndrome, Abt-Letterer-Siwe syndrome and Eosinophilic granuloma. "
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    • "clustering of LCH are points in favour of the neoplastic theory. On the other hand, the benign cytology of LCH cells, the indolent clinical course of most LCH cases as well as the lack of clonality in pulmonary LCH may be considered arguments for a reactive nature of LCH [12]. These observations point to a heterogeneous etiology of LCH. "
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