Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice

Hsiu-Jung Liao; I-Tsu Chyuan; Chien-Sheng Wu; Shu-Wha Lin; Kun-Hung Chen; Hwei-Fang Tsai; Ping-Ning Hsu

doi:10.1093/rheumatology/keu481

Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice

Rheumatology (Oxford). 2015 Jul;54(7):1317-26. doi: 10.1093/rheumatology/keu481. Epub 2015 Jan 18.

Authors

Hsiu-Jung Liao¹, I-Tsu Chyuan¹, Chien-Sheng Wu¹, Shu-Wha Lin¹, Kun-Hung Chen¹, Hwei-Fang Tsai², Ping-Ning Hsu³

Affiliations

¹ 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.
² 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.
³ 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.

PMID: 25602062
DOI: 10.1093/rheumatology/keu481

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.

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.

Keywords: IL-1; PSTPIP2; SAPHO syndrome; neutrophil.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acquired Hyperostosis Syndrome / metabolism*
Acquired Hyperostosis Syndrome / pathology*
Adaptor Proteins, Signal Transducing / deficiency*
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Animals
Bone Marrow / pathology
Cell Movement*
Chemokines / metabolism
Cytoskeletal Proteins / deficiency*
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism
Disease Models, Animal
Hyperostosis / metabolism
Hyperostosis / pathology
Immunity, Innate
Interleukin-1 / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils / pathology*
Osteitis / metabolism
Osteitis / pathology
Phenotype*
Synovitis / metabolism
Synovitis / pathology

Substances

Adaptor Proteins, Signal Transducing
Chemokines
Cytoskeletal Proteins
Interleukin-1
Pstpip2 protein, mouse