Deficient invariant natural killer T cells had impaired regulation on osteoclastogenesis in myeloma bone disease.
Deficient invariant natural killer T cells had impaired regulation on osteoclastogenesis in myeloma bone disease.
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DOI：
10.1111/jcmm.13554
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发表时间：
2018-05
影响因子：
5.3
通讯作者：
Fu R
中科院分区：
文献类型：
--
作者：
Jiang F;Liu H;Liu Z;Yan S;Chen J;Shao Q;Li L;Song J;Wang G;Shao Z;Fu R
最近的研究表明，不变的自然杀伤T细胞(INKT)参与了破骨细胞生成的调控。而iNKT细胞在骨髓瘤骨病(MBD)中的作用尚不清楚。在我们的研究中，用流式细胞仪检测iNKT细胞的数量及其产生的细胞因子水平。外周血单个核细胞经α-GalCer或RANKL体外活化后，可诱导出iNKT细胞和破骨细胞。用RT-PCR和ELISA法分别检测基因表达和细胞因子水平。结果表明，初诊MM患者iNKT细胞数量和iNKT细胞产生干扰素-γ均显著降低，且均与骨病严重程度呈负相关。体外培养的健康对照破骨细胞经α-GalCer刺激后表达下调，而在α-GalCer刺激前后无明显变化，提示iNKT细胞对破骨细胞生成的调控功能受损。此外，干扰素-γ的产生下调了破骨细胞相关基因的表达，从而抑制了iNKT细胞的破骨细胞生成。总之，α-GalCer刺激的iNKT细胞在调节破骨细胞生成中的作用在多发性骨髓病中受到损害，这是iNKT细胞功能障碍的结果。
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.
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影响因子：
4
作者：
D'Amelio, P.;Tamone, C.;Isaia, G. C.
通讯作者：
Isaia, G. C.
影响因子：
--
作者：
Oranger A;Carbone C;Izzo M;Grano M
通讯作者：
Grano M
DOI：
10.1016/j.clim.2010.12.010
发表时间：
2011-08
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Dhodapkar MV;Richter J
通讯作者：
Richter J
影响因子：
20.3
作者：
Richter, Joshua;Neparidze, Natalia;Dhodapkar, Madhav V.
通讯作者：
Dhodapkar, Madhav V.
影响因子：
--
作者：
Brunetti G;Rizzi R;Oranger A;Gigante I;Mori G;Taurino G;Mongelli T;Colaianni G;Di Benedetto A;Tamma R;Ingravallo G;Napoli A;Faienza MF;Mestice A;Curci P;Specchia G;Colucci S;Grano M
通讯作者：
Grano M