Activated Invariant NKT Cells Regulate Osteoclast Development and Function
Activated Invariant NKT Cells Regulate Osteoclast Development and Function
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DOI：
10.4049/jimmunol.1002353
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发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Karadimitris, Anastasios
中科院分区：
文献类型：
--
作者：
Hu, Ming;Bassett, J. H. Duncan;Karadimitris, Anastasios
不变NKT（iNKT）细胞通过激活髓样树突细胞和巨噬细胞以及通过增强其共享髓样祖细胞的克隆形成、分化和排出来调节先天性和适应性免疫应答。由于这些相同的祖细胞产生破骨细胞（OC），破骨细胞也介导造血祖细胞的流出并协调骨重建，因此我们假设iNKT细胞将其骨髓细胞调节作用扩展到OC的发育和功能。在这项研究中，我们报告说，选择性激活iNKT细胞的α-半乳糖神经酰胺导致骨髓细胞的出口，增强OC祖细胞和前体的发展，修改髓内动力学成熟OC，并提高其吸收活性。OC祖细胞活性受TNF-α的正调节，受IFN-γ的负调节，但不依赖于IL-4和IL-17。这些数据证明了iNKT细胞在免疫激活条件下将破骨细胞生成与髓样细胞流出偶联的新作用。免疫学杂志，2011，186：2910-2917。
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 alpha-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-alpha and negatively regulated by IFN-gamma, 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. The Journal of Immunology, 2011, 186: 2910-2917.