Deficient invariant natural killer T cells had impaired regulation on osteoclastogenesis in myeloma bone disease

Abstract

Recent research showed that invariant natural killer T (iNKT) cells take part in the regulation of osteoclastogenesis. While the role of iNKT cells in myeloma bone disease (MBD) remains unclear. In our study, the quantity of iNKT cells and the levels of cytokines produced by them were measured by flow cytometry. iNKT cells and osteoclasts were induced from peripheral blood mononuclear cells after activation by α-GalCer or RANKL in vitro. Then, gene expressions and the levels of cytokines were determined by RT-PCR and ELISA, respectively. The results showed that the quantity of iNKT and production of IFN-γ by iNKT cells were significantly decreased in newly diagnosed MM (NDMM), and both negatively related with severity of bone disease. Then, the osteoclasts from healthy controls were cultured in vitro and were found to be down-regulated after α-GalCer-stimulated, while there was no significant change with or without α-GalCer in NDMM patients, indicating that the regulation of osteoclastogenesis by iNKT cells was impaired. Furthermore, the inhibition of osteoclastogenesis by iNKT cells was regulated by IFN-γ production, which down-regulated osteoclast-associated genes. In conclusion, the role of α-GalCer-stimulated iNKT cells in regulation of osteoclastogenesis was impaired in MBD, as a result of iNKT cell dysfunction.

Keywords: invariant natural killer T cell; myeloma bone disease; osteoclastogenesis; α-galactosylceramide.