title: Murine dendritic cell transdifferentiation into osteoclasts is differentially regulated by innate and adaptive cytokines.
abstract: Dendritic cells (DC) are the mononuclear cells that initiate adaptive immune responses. Osteoclasts (OC) are the multinucleated giant cells that resorb bone. As previously described for human conventional DC (cDC), we demonstrate that murine cDC, either in vitro generated from Fms-like tyrosine kinase 3 (Flt3)+ bone marrow progenitors or ex vivo purified from spleen, are able to develop into OC in response to M-CSF and receptor activator of NF-kappaB ligand (RANKL) in vitro. This transdifferentiation is driven by the immune environment that controls cDC maturation, cell fusion, tartrate-resistant acid phosphatase (TRAP) and bone resorption activities. Only immature cDC have the capacity to become OC since mature cDC or plasmacytoid DC do not. Additions of the pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, or human rheumatoid synovial fluid, increase murine cDC transdifferentiation into OC, whereas IFN-alpha inhibits it. The adaptive cytokine, IFN-gamma, inhibits cDC fusion while IL-4 increases it. IL-2, IFN-gamma and IL-4 inhibit TRAP and bone resorption activities contrary to IL-10, which enhances both activities. A putative new "immune multinucleated giant cell" unable to resorb bone, which is formed owing to IL-4, is underlined. The future analysis of cDC transdifferentiation into OC in murine models of inflammatory arthritis will give us the quantitative importance of this phenomenon in vivo.
authors.affiliation: INSERM, U503, Université de Lyon, Université Lyon 1, IFR128, Lyon, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Speziani
authors.forename: Aymeric
authors.initials: A
authors.lastname: Rivollier
authors.forename: Anne
authors.initials: A
authors.lastname: Gallois
authors.forename: Fabienne
authors.initials: F
authors.lastname: Coury
authors.forename: Marlène
authors.initials: M
authors.lastname: Mazzorana
authors.forename: Olga
authors.initials: O
authors.lastname: Azocar
authors.forename: Monique
authors.initials: M
authors.lastname: Flacher
authors.forename: Chantal
authors.initials: C
authors.lastname: Bella
authors.forename: Jacques
authors.initials: J
authors.lastname: Tebib
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: Chantal
authors.initials: C
authors.lastname: Rabourdin-Combe
authors.forename: Christine
authors.initials: C
authors.lastname: Delprat
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006131:Growth Inhibitors / Q000502:physiology*; D007110:Immunity, Active; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D006131:Growth Inhibitors