title: Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Hsiu-Jung
authors.initials: HJ
authors.lastname: Liao
authors.affiliation: 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.
authors.forename: I-Tsu
authors.initials: IT
authors.lastname: Chyuan
authors.affiliation: 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.
authors.forename: Chien-Sheng
authors.initials: CS
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Shu-Wha
authors.initials: SW
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Kun-Hung
authors.initials: KH
authors.lastname: Chen
authors.affiliation: 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 hftsai8635@yahoo.com.tw.
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tsai
authors.affiliation: 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.
authors.forename: Ping-Ning
authors.initials: PN
authors.lastname: Hsu
mesh_terms: D020083:Acquired Hyperostosis Syndrome / Q000378:metabolism* / Q000473:pathology*; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015576:Hyperostosis / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology*; D010000:Osteitis / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D013585:Synovitis / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; D003598:Cytoskeletal Proteins; D007375:Interleukin-1; C486383:Pstpip2 protein, mouse
keywords: IL-1; PSTPIP2; SAPHO syndrome; neutrophil