title: Activated invariant NKT cells regulate osteoclast development and function.
abstract: Invariant NKT (iNKT) cells modulate innate and adaptive immune responses through activation of myeloid dendritic cells and macrophages and via enhanced clonogenicity, differentiation, and egress of their shared myeloid progenitors. Because these same progenitors give rise to osteoclasts (OCs), which also mediate the egress of hematopoietic progenitors and orchestrate bone remodeling, we hypothesized that iNKT cells would extend their myeloid cell regulatory role to the development and function of OCs. In this study, we report that selective activation of iNKT cells by α-galactosylceramide causes myeloid cell egress, enhances OC progenitor and precursor development, modifies the intramedullary kinetics of mature OCs, and enhances their resorptive activity. OC progenitor activity is positively regulated by TNF-α and negatively regulated by IFN-γ, but is IL-4 and IL-17 independent. These data demonstrate a novel role of iNKT cells that couples osteoclastogenesis with myeloid cell egress in conditions of immune activation.
authors.affiliation: Center for Hematology, Hammersmith Hospital, Imperial College London, London W12 0NN, United Kingdom.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.forename: J H Duncan
authors.initials: JH
authors.lastname: Bassett
authors.forename: Lynett
authors.initials: L
authors.lastname: Danks
authors.forename: Peter G T
authors.initials: PG
authors.lastname: Howell
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Spanoudakis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kotsianidis
authors.forename: Alan
authors.initials: A
authors.lastname: Boyde
authors.forename: Graham R
authors.initials: GR
authors.lastname: Williams
authors.forename: Nikki
authors.initials: N
authors.lastname: Horwood
authors.forename: Irene A G
authors.initials: IA
authors.lastname: Roberts
authors.forename: Anastasios
authors.initials: A
authors.lastname: Karadimitris
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D053245:RANK Ligand / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma