Laboratory of Host Defense, Osaka University, Osaka, Japan.
Immunity. 2012 Dec 14;37(6):1024-36. doi: 10.1016/j.immuni.2012.08.022. Epub 2012 Nov 29.
Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous in vitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered its crucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses its expression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in in vivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation.
Jdp2 是一个 AP-1 家族转录因子，可调节组蛋白的表观遗传状态。先前的体外研究表明 Jdp2 参与破骨细胞的生成。然而，Jdp2 在体内的作用及其多效性功能在很大程度上尚不清楚。在这里，我们生成了 Jdp2(-/-) 小鼠，并发现其不仅在骨代谢中具有关键作用，而且在中性粒细胞的分化中也具有关键作用。Jdp2(-/-) 小鼠表现出破骨细胞生成受损导致的骨质硬化症。Jdp2(-/-) 中性粒细胞形态正常，但 Ly6G 的表面表达、杀菌功能和凋亡受损。我们还发现 ATF3 是中性粒细胞分化的抑制剂，而 Jdp2 通过抑制组蛋白乙酰化直接抑制其表达。引人注目的是，Jdp2(-/-) 小鼠对金黄色葡萄球菌和白色念珠菌感染高度敏感。因此，Jdp2 通过调节破骨细胞和中性粒细胞的分化，在体内骨稳态和宿主防御中发挥关键作用。
