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.
Okuzawa
Chie
C
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan.
Kaneko
Yoriaki
Y
Murata
Yoji
Y
Miyake
Astuko
A
Saito
Yasuyuki
Y
Okajo
Jun
J
Tomizawa
Takeshi
T
Kaneko
Yuka
Y
Okazawa
Hideki
H
Ohnishi
Hiroshi
H
Matozaki
Takashi
T
Nojima
Yoshihisa
Y
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D024043:Collagen Type II; D016207:Cytokines; D007074:Immunoglobulin G; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic