Dendritic Cells Cause Bone Lesions in a New Mouse Model of Histiocytosis.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_B4230F15A8A5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Dendritic Cells Cause Bone Lesions in a New Mouse Model of Histiocytosis.
Périodique
Plos One
Auteur(s)
Grosjean F., Nasi S., Schneider P., Chobaz V., Liu A., Mordasini V., Moullec K., Vezzoni P., Lavanchy C., Busso N., Acha-Orbea H., Ehirchiou D.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
10
Numéro
8
Pages
e0133917
Langue
anglais
Résumé
Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal accumulation of dendritic Langerhans cells, which is often accompanied by osteolytic lesions. It has been reported that osteoclast-like cells play a major role in the pathogenic bone destruction seen in patients with LCH and these cells are postulated to originate from the fusion of DCs. However, due to the lack of reliable animal models the pathogenesis of LCH is still poorly understood. In this study, we have established a mouse model of histiocytosis- recapitulating human disease for osteolytic lesions seen in LCH patients. At 12 weeks after birth, severe bone lesions were observed in our multisystem histiocytosis (Mushi) model, when CD8α conventional dendritic cells (DCs) are transformed (MuTuDC) and accumulate. Most importantly, our study demonstrates that bone loss in LCH can be accounted for the transdifferentiation of MuTuDCs into functional osteoclasts both in vivo and in vitro. Moreover, we have shown that injected MuTuDCs reverse the osteopetrotic phenotype of oc/oc mice in vivo. In conclusion, our results support a crucial role of DCs in bone lesions in histiocytosis patients. Furthermore, our new model of LCH based on adoptive transfer of MuTuDC lines, leading to bone lesions within 1-2 weeks, will be an important tool for investigating the pathophysiology of this disease and ultimately for evaluating the potential of anti-resorptive drugs for the treatment of bone lesions.
Mots-clé
Animals, Bone Density Conservation Agents/therapeutic use, Bone and Bones/drug effects, Bone and Bones/pathology, Cell Line, Cell Transdifferentiation, Dendritic Cells/pathology, Diphosphonates/therapeutic use, Disease Models, Animal, Histiocytosis, Langerhans-Cell/complications, Histiocytosis, Langerhans-Cell/pathology, Humans, Langerhans Cells/pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Osteoclasts/pathology, Osteolysis/complications, Osteolysis/pathology, Osteoprotegerin/therapeutic use
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/08/2015 15:42
Dernière modification de la notice
20/08/2019 16:22
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