Resistance to collagen-induced arthritis in SHPS-1 mutant mice
Resistance to collagen-induced arthritis in SHPS-1 mutant mice
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DOI：
10.1016/j.bbrc.2008.04.124
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发表时间：
2008-07-04
影响因子：
3.1
通讯作者：
Nojima, Yoshihisa
中科院分区：
文献类型：
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作者：
Okuzawa, Chie;Kaneko, Yoriaki;Nojima, Yoshihisa
SHPS-1是一种跨膜蛋白，通过其胞质区域结合蛋白酪氨酸磷酸酶SHP-1和SHP-2，并在树突状细胞和巨噬细胞上大量表达。在这里，我们表明，表达突变形式的SHPS-1的小鼠未能发展II型胶原（CII）诱导的关节炎（CIA），类风湿性关节炎的模型在人类。免疫野生型小鼠关节炎爪的组织学检查显示，软骨被破坏与显着的单核细胞浸润，而只有轻微的细胞浸润中观察到免疫SHPS-1突变小鼠。一致地，免疫的SHPS-1突变小鼠中CII特异性IgG和IgG 2a以及IL-1 β的血清水平与野生型小鼠相比明显降低。与野生型细胞相比，来自免疫的SHPS-1突变小鼠的T细胞的CII诱导的增殖和细胞因子的产生减少。这些结果表明SHPS-1在CIA的发生发展中是必不可少的。(C)2008年爱思唯尔公司All rights reserved.
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. (C) 2008 Elsevier Inc. All rights reserved.