PSTPIP2基因缺陷小鼠中性粒细胞浸润增加、白细胞介素-1生成及类滑膜炎-痤疮-脓疱病-骨肥厚-骨炎综合征样表型
Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice.
作者信息
Liao Hsiu-Jung, Chyuan I-Tsu, Wu Chien-Sheng, Lin Shu-Wha, Chen Kun-Hung, Tsai Hwei-Fang, Hsu Ping-Ning
机构信息
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
出版信息
Rheumatology (Oxford). 2015 Jul;54(7):1317-26. doi: 10.1093/rheumatology/keu481. Epub 2015 Jan 18.
OBJECTIVE
Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is involved in macrophage activation, neutrophil motility and osteoclast differentiation. However, the role of PSTPIP2 in inflammation and autoinflammatory diseases is still not clear. In this study, we generated PSTPIP2 knockout (Pstpip2(-/-)) mice to investigate its phenotype and role in autoinflammatory diseases.
METHODS
We constructed a Pstpip2-targeting vector and generated Pstpip2(-/-) mice. The phenotype and immunopathology of Pstpip2(-/-) mice were analysed.
RESULTS
All Pstpip2(-/-) mice developed paw swelling, synovitis, hyperostosis and osteitis, resembling SAPHO syndrome, an inflammatory disorder of the bone, skin and joints. Multifocal osteomyelitis was found in inflamed paws, with increased macrophage and marked neutrophil infiltrations in the bone, joint and skin. Profound osteolytic lesions with markedly decreased bone volume density developed in paws and limbs. Neutrophil-attracting chemokines and IL-1β were markedly elevated in inflamed tissues.
CONCLUSION
Our study suggests that PSTPIP2 could play a role in innate immunity and development of autoinflammatory bone disorders, and may be associated with the pathogenesis of human SAPHO syndrome.
目的
脯氨酸 - 丝氨酸 - 苏氨酸磷酸酶相互作用蛋白2（PSTPIP2）参与巨噬细胞活化、中性粒细胞运动和破骨细胞分化。然而，PSTPIP2在炎症和自身炎症性疾病中的作用仍不清楚。在本研究中，我们构建了PSTPIP2基因敲除（Pstpip2(-/-)）小鼠，以研究其在自身炎症性疾病中的表型和作用。
方法
我们构建了靶向Pstpip2的载体并培育出Pstpip2(-/-)小鼠。对Pstpip2(-/-)小鼠的表型和免疫病理学进行了分析。
结果
所有Pstpip2(-/-)小鼠均出现爪肿胀、滑膜炎、骨质增生和骨炎，类似于滑膜炎、痤疮、脓疱病、骨肥厚、骨炎综合征（SAPHO综合征），一种骨骼、皮肤和关节的炎症性疾病。在发炎的爪子中发现多灶性骨髓炎，在骨骼、关节和皮肤中巨噬细胞增多且有明显的中性粒细胞浸润。爪子和四肢出现严重的溶骨性病变，骨体积密度明显降低。在发炎组织中，吸引中性粒细胞的趋化因子和白细胞介素 - 1β明显升高。
结论
我们的研究表明，PSTPIP2可能在先天免疫和自身炎症性骨病的发展中起作用，并且可能与人类SAPHO综合征的发病机制有关。
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