Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 publication

DOI

10.4049/jimmunol.1002353

Type

Journal article

Journal

J Immunol

Publication Date

01/03/2011

Volume

186

Pages

2910 - 2917

Keywords

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