Villa Anna, Vezzoni Paolo, Frattini Annalisa
Istituto Tecnologie Biomediche, CNR, Segrate, Italy.
Curr Opin Allergy Clin Immunol. 2006 Dec;6(6):421-7. doi: 10.1097/01.all.0000246620.26623.5b.
This review focuses on human and murine pathologies involving both osteoclasts and immune cells. These diseases have been relevant to the discovery of novel interactions and pathways shared between these two types of cells.
Interactions between immune cells and osteoclasts were originally shown in murine models by gene targeting of molecules involved in the early steps of osteoclast differentiation, since receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and TNFR-associated factor 6 knockout mice bore abnormalities of both bone resorption and immune system. Subsequently, osteoclast stimulation by RANKL secreted by lymphocytes in autoimmune diseases, such as rheumatoid arthritis, was found. More recently, the identification of immunoreceptor tyrosine-based activation motif receptors and adaptors important for both dendritic cells and osteoclast function has established a link between innate and adaptive immunity and bone. Finally, osteoclasts are also important for hematopoietic stem-cell mobilization, providing a further level of regulation of lymphoid cells.
These findings open up a new field of research, osteoimmunology, which will unravel previously unsuspected links between bone remodelling and the immune response.
本综述聚焦于涉及破骨细胞和免疫细胞的人类及小鼠病理学。这些疾病与发现这两类细胞之间新的相互作用和共同途径相关。
免疫细胞与破骨细胞之间的相互作用最初在小鼠模型中通过对破骨细胞分化早期步骤中涉及分子的基因靶向研究得以展现，因为核因子κB受体活化因子配体（RANKL）、RANK和肿瘤坏死因子受体相关因子6基因敲除小鼠存在骨吸收和免疫系统异常。随后，发现在类风湿关节炎等自身免疫性疾病中淋巴细胞分泌的RANKL可刺激破骨细胞。最近，对树突状细胞和破骨细胞功能均重要的基于免疫受体酪氨酸的活化基序受体和衔接蛋白的鉴定，在固有免疫和适应性免疫与骨之间建立了联系。最后，破骨细胞对造血干细胞动员也很重要，为淋巴细胞提供了进一步的调控水平。
这些发现开辟了一个新的研究领域——骨免疫学，它将揭示骨重塑与免疫反应之间以前未被怀疑的联系。
