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

Journal Article · Fri Jul 04 04:00:00 EDT 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.04.124· OSTI ID:21143745

Okuzawa, Chie; Kaneko, Yoriaki ^[1]; Murata, Yoji; Miyake, Astuko ^[2]; Saito, Yasuyuki; Okajo, Jun; Tomizawa, Takeshi ^[1]; Kaneko, Yuka; Okazawa, Hideki; Ohnishi, Hiroshi ^[2]; Matozaki, Takashi ^[2]; Nojima, Yoshihisa ^[1]

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1. Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511 (Japan)
2. Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512 (Japan)

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-1{beta} 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.

• OSTI ID: 21143745
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 371; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARTILAGE
COLLAGEN
DENDRITES
LYMPHOKINES
MACROPHAGES
MICE
MUTANTS
PHOSPHATASES
RHEUMATIC DISEASES
TYROSINE