title: Dendritic Cells Cause Bone Lesions in a New Mouse Model of Histiocytosis.
abstract: 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.
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Grosjean
authors.affiliation: DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Epalinges, Switzerland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Nasi
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.affiliation: DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Epalinges, Switzerland.
authors.forename: Véronique
authors.initials: V
authors.lastname: Chobaz
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mordasini
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Kristell
authors.initials: K
authors.lastname: Moullec
authors.affiliation: UOS/IRGB, Milan Unit, CNR, via Fantoli 15/16-20138 Milano, and Humanitas Research Center, Rozzano Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vezzoni
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Lavanchy
authors.affiliation: DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Epalinges, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Driss
authors.initials: D
authors.lastname: Ehirchiou
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002460:Cell Line; D054338:Cell Transdifferentiation; D003713:Dendritic Cells / Q000473:pathology*; D004164:Diphosphonates / Q000627:therapeutic use; D004195:Disease Models, Animal; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000473:pathology*; D006801:Humans; D007801:Langerhans Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000473:pathology; D010014:Osteolysis / Q000150:complications / Q000473:pathology* / Q000517:prevention & control; D053244:Osteoprotegerin / Q000627:therapeutic use
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053244:Osteoprotegerin