Resistance to collagen-induced arthritis in SHPS-1 mutant mice
Chie Okuzawa1, Yoriaki Kaneko, Yoji Murata
1Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan.
Abstract:
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.
Insights
SHPS-1 protein is crucial for developing collagen-induced arthritis (CIA), a rheumatoid arthritis model. Mutant SHPS-1 mice showed significantly reduced arthritis, indicating SHPS-1
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- SHPS-1 is a transmembrane protein expressed on dendritic cells and macrophages.
- It interacts with protein tyrosine phosphatases SHP-1 and SHP-2.
- Rheumatoid arthritis involves immune cell infiltration and cartilage destruction.
Purpose of the Study:
- To investigate the role of SHPS-1 in the development of collagen-induced arthritis (CIA).
Main Methods:
- Utilized mutant SHPS-1 mice in a collagen-induced arthritis (CIA) model.
- Performed histological examinations of arthritic paws.
- Measured serum levels of anti-CII antibodies (IgG, IgG2a) and IL-1beta.
- Assessed T cell proliferation and cytokine production in response to CII.
Main Results:
- Mice with mutant SHPS-1 failed to develop CIA.
- Arthritic paws showed reduced cartilage destruction and mononuclear cell infiltration in mutant mice.
- Serum levels of anti-CII IgG, IgG2a, and IL-1beta were significantly lower in mutant mice.
- T cell responses to CII were diminished in mutant mice.
Conclusions:
- SHPS-1 is essential for the development of collagen-induced arthritis (CIA).
- SHPS-1 plays a critical role in mediating immune responses involved in rheumatoid arthritis pathogenesis.
