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Activated invariant NKT cells regulate osteoclast development and function
Ming Hu1, J H Duncan Bassett, Lynett Danks
1Center for Hematology, Hammersmith Hospital, Imperial College London, London W12 0NN, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|February 1, 2011
Summary
Invariant natural killer T (iNKT) cells regulate myeloid cell egress and osteoclast development. This study reveals iNKT cell activation enhances osteoclast precursor development and bone remodeling functions.
Area of Science:
- Immunology
- Cell Biology
- Bone Biology
Background:
- Invariant natural killer T (iNKT) cells are crucial immune regulators.
- Myeloid progenitors give rise to both immune cells and osteoclasts (OCs).
- Osteoclasts are key in bone remodeling and hematopoietic progenitor egress.
Purpose of the Study:
- To investigate the role of iNKT cells in osteoclast development and function.
- To determine if iNKT cells extend their myeloid regulatory role to osteoclastogenesis.
- To explore the link between iNKT cell activation and myeloid cell egress.
Main Methods:
- Selective activation of iNKT cells using α-galactosylceramide.
- Analysis of myeloid cell egress and osteoclast progenitor/precursor development.
- Assessment of mature osteoclast kinetics and resorptive activity.
- Investigation of cytokine regulation (TNF-α, IFN-γ, IL-4, IL-17) of osteoclast progenitor activity.
Main Results:
- iNKT cell activation induced myeloid cell egress.
- Enhanced development of osteoclast progenitors and precursors was observed.
- Modulation of mature osteoclast intramedullary kinetics and increased resorptive activity.
- Osteoclast progenitor activity was positively regulated by TNF-α and negatively by IFN-γ, independent of IL-4 and IL-17.
Conclusions:
- Invariant NKT cells play a novel role in regulating osteoclastogenesis.
- iNKT cell activation couples osteoclast development with myeloid cell egress.
- This highlights a new mechanism linking immune activation to bone remodeling processes.
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