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

Journal of Cellular and Molecular Medicine - Tập 22 Số 5 - Trang 2706-2716 - 2018
Fengjuan Jiang1, Hui Liu2, Zhaoyun Liu2, Siyang Yan1, Jin Chen2, Qing Shao2, Lijuan Li1,2, Jia Song2, Guojin Wang2, Zonghong Shao1,2, Rong Fu1,2
1Department of Graduate School, Tianjin Medical University, Tianjin, China
2Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China

Tóm tắt

AbstractRecent 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 RTPCR 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.

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