Resistance to collagen-induced arthritis in SHPS-1 mutant mice.


SHPS-1 is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on dendritic cells and macrophages. Here we show that mice expressing a mutant form of SHPS-1 fail to develop type-II collagen (CII)-induced arthritis (CIA), a model for rheumatoid arthritis in humans. Histological examinations of the arthritic paws from immunized wild-type mice revealed that cartilage was destroyed in association with marked mononuclear cell infiltration, while only mild cell infiltration was observed in immunized SHPS-1 mutant mice. Consistently, the serum levels of both IgG and IgG2a specific to CII and of IL-1beta in immunized SHPS-1 mutant mice were markedly reduced compared with those apparent for wild-type mice. The CII-induced proliferation of, and production of cytokines by, T cells from immunized SHPS-1 mutant mice were reduced compared to wild-type cells. These results suggest that SHPS-1 is essential for development of CIA.

DOI: 10.1016/j.bbrc.2008.04.124


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@article{Okuzawa2008ResistanceTC, title={Resistance to collagen-induced arthritis in SHPS-1 mutant mice.}, author={Chie Okuzawa and Yoriaki Kaneko and Yoji Murata and Astuko Miyake and Yasuyuki Saito and Jun Okajo and Takeshi Tomizawa and Yuka Kaneko and Hideki Okazawa and Hiroshi Ohnishi and Takashi Matozaki and Yoshihisa Nojima}, journal={Biochemical and biophysical research communications}, year={2008}, volume={371 3}, pages={561-6} }