Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss.
Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss.
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DOI：
10.1038/ncomms7651
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发表时间：
2015-03-31
影响因子：
16.6
通讯作者：
Schett, Georg
中科院分区：
文献类型：
--
作者：
Harre, Ulrike;Lang, Stefanie C.;Pfeifle, Rene;Rombouts, Yoann;Fruhbeisser, Sabine;Amara, Khaled;Bang, Holger;Lux, Anja;Koeleman, Carolien A.;Baum, Wolfgang;Dietel, Katharina;Groehn, Franziska;Malmstroem, Vivianne;Klareskog, Lars;Kroenke, Gerhard;Kocijan, Roland;Nimmerjahn, Falk;Toes, Rene E. M.;Herrmann, Martin;Scherer, Hans Ulrich;Schett, Georg
免疫球蛋白G（IgG）唾液酸化是决定促炎或抗炎Fcγ受体（FcγR）参与和免疫应答方向的关键检查点。IgG唾液酸化是否影响破骨细胞分化和随后的骨结构尚未确定，但可能代表免疫激活和骨丢失之间的重要联系。在这里，我们证明，去唾液酸化，但不唾液酸化，免疫复合物增强破骨细胞在体外和体内。此外，我们发现随机IgG和特异性IgG自身抗体的Fc唾液酸化状态决定了类风湿关节炎患者的骨结构。根据这些发现，用唾液酸前体N-乙酰甘露糖胺（ManNAc）治疗的小鼠（导致IgG唾液酸化增加）对炎性骨丢失不太敏感。总之，我们的研究结果提供了一种免疫反应影响人类骨骼的新机制，以及一种抑制免疫介导的骨丢失的创新治疗方法。 IgG糖部分调节免疫复合物与其Fcγ受体的结合，导致促炎或抗炎反应。这项研究表明，IgG唾液酸化也影响小鼠和人类的破骨细胞生成和骨量，确定了骨骼和免疫系统之间的新联系。
Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss. The IgG sugar moiety modulates the binding of immune complexes to their Fcγ receptors resulting in pro- or anti-inflammatory response. This study shows that IgG sialylation also affects osteoclastogenesis and bone mass in mice and humans, identifying a new link between bone and the immune system.
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