Activated invariant NKT cells regulate osteoclast development and function

Ming Hu, J H Duncan Bassett, Lynett Danks, Peter G T Howell, Ke Xu, Emmanouil Spanoudakis, Ioannis Kotsianidis, Alan Boyde, Graham R Williams, Nikki Horwood, Irene A G Roberts, Anastasios Karadimitris

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34 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2910-2917
Number of pages8
JournalJournal of Immunology
Issue number5
Early online date15 Feb 2011
Publication statusPublished - 1 Mar 2011


  • Animals
  • Cell Differentiation/immunology
  • Cell Movement/immunology
  • Dendritic Cells/cytology
  • Down-Regulation/immunology
  • Interferon-gamma/physiology
  • Lymphocyte Activation/immunology
  • Macrophage Colony-Stimulating Factor/physiology
  • Macrophages/cytology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells/cytology
  • Natural Killer T-Cells/cytology
  • Osteoclasts/cytology
  • RANK Ligand/physiology
  • Stem Cells/cytology
  • Tumor Necrosis Factor-alpha/physiology
  • Up-Regulation/immunology

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