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

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.

authors

Okuzawa C,Kaneko Y,Murata Y,Miyake A,Saito Y,Okajo J,Tomizawa T,Kaneko Y,Okazawa H,Ohnishi H,Matozaki T,Nojima Y

doi

10.1016/j.bbrc.2008.04.124

subject

Has Abstract

pub_date

2008-07-04 00:00:00

pages

561-6

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(08)00807-3

journal_volume

371

pub_type

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