Volume 14 Supplement 1

Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Open Access

Postnatal Syk deletion in mice clarifies the function of Syk in an anti-collagen antibody-induced arthritis model

  • Naoko Ozaki1, 2,
  • Shinobu Suzuki2,
  • Hiromitsu Hara1 and
  • Hiroki Yoshida1
Arthritis Research & Therapy201214(Suppl 1):O22

DOI: 10.1186/ar3577

Published: 29 February 2012

Spleen tyrosine kinase (Syk) is a cytoplasmic protein expressed mainly in immune cells including macrophages and neutrophils and is associated with receptors containing an immunoreceptor tyrosine-based activation motif (ITAM), such as Fcγ receptors. As Syk-mediated signaling plays an important role in activation of immune responses, to investigate whether specific interruption of Syk-mediated signaling can affect the development of rheumatoid arthritis (RA), we used tamoxifen-induced conditional Syk-KO mice (iSyk KO) to evaluate the importance of Syk on disease development. Using a collagen antibody-induced arthritis model (CAIA), iSyk KO mice showed significantly attenuated disease severity compared to Syk non-deleted mice (Figure 1). Although iSyk KO mice contained reduced B cell numbers after deletion of Syk in adulthood, B cells are not required for arthritis development in CAIA, as demonstrated by using muMT mice which lack B cells. On the other hand, Syk-deficient macrophages produced less MCP-1 and IL-6 than Syk-sufficient cells after FcR ligation, which can account for the absence of a pronounced accumulation of neutrophils and macrophages in the joints of iSyk KO mice. Our results demonstrate that Syk in macrophages is likely a key player in antibody-induced arthritis, mediating the release of pro-inflammatory cytokines and chemokines after macrophages bind anti-collagen antibody, and indicate that Syk is a promising target for arthritis therapy.
https://static-content.springer.com/image/art%3A10.1186%2Far3577/MediaObjects/13075_2012_Article_3324_Fig1_HTML.jpg
Figure 1

Arthritis development in iSyk KO mice. Arthritis was induced by i.p. administration of anti-collagen Ab followed by LPS. Arthritis score was monitored. *; P < 0.001, **; P < 0.01.

Authors’ Affiliations

(1)
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University
(2)
Department of Molecular & Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer Ingelheim Co Ltd

Copyright

© Ozaki et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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