Activated invariant NKT cells regulate osteoclast development and function |
| |
Authors: | Hu Ming Bassett J H Duncan Danks Lynett Howell Peter G T Xu Ke Spanoudakis Emmanouil Kotsianidis Ioannis Boyde Alan Williams Graham R Horwood Nikki Roberts Irene A G Karadimitris Anastasios |
| |
Institution: | Center for Hematology, Hammersmith Hospital, Imperial College London, London W12 0NN, United Kingdom. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|