Study of Dendritic Cell-Derived Multinucleated Giant Cells in Langerhans Cell Histiocytosis
Christine Servet-Delprat PhD
Molecular Immunobiology Clinic; INSERM – Lyon, France
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LCH may affect any age group, from the newborn to the elderly, but clinical features, pathogenesis, and treatment outcome derives from the pediatric experience. The incidence for LCH of around 1:200,000 children per year, peaks at 1-3 years. LCH is an ‘orphan’ disease that belongs to the Histiocytoses. Besides visceral organ involvement, 80% of patients with multisystem disease develop bone lesions; the cells that resorb bone are myeloid-derived multinucleated giant cell (MGC) called osteoclasts.
The course of LCH is often unpredictable, varying from spontaneous regression and resolution to rapid progression and death or repeated recurrence and recrudescence with a considerable risk of permanent sequelae since tumors destroy the tissue where they grow. Inside tumors, multinucleated giant cells (MGC) express different phenotypes, depending on the tissue they colonize. The origin and the functions of these MGC are unknown. However we demonstrated that normal DC are able to fuse and transdifferentiate into osteoclasts. It is thus reasonable to propose that MGC observed in LCH lesion come from the fusion of pathogenic DC and are able to destroy tissues, especially bone matrix. MGC would consequently be responsible for the sequelae associated to this disease, sometimes leading to a fatal issue.
The objective is to study the DC-derived multinucleated giant cells in LCH. The aim is to design therapeutic agents able to prevent DC fusion and their transdifferentiation into osteoclasts. Thus, monoclonal antibodies able to block formation and/or function of DC-derived MGC will be produced. The hope is that preventing MGC formation from LCH-DC will abrogate or at least reduce tissue destruction in all LCH lesions.