The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis
The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis
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DOI：
10.1093/intimm/dxh045
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Hirano, T
中科院分区：
文献类型：
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作者：
Ishihara, K;Sawa, S;Hirano, T
风湿性关节炎（RA）是一种多基因自身免疫性疾病。自身免疫是遗传和环境因素协同作用的结果。我们通过在C57 BL/6背景下杂交两种RA小鼠模型，即gp 130突变敲入小鼠（gp 130（F759/F759））和HTLV-1 pX转基因小鼠（pX-Tg），产生了一种双突变小鼠，其对关节炎具有抗性。这些小鼠自发地发展出严重的关节炎，比gp 130（F759/F759）小鼠的发病早得多，并且比pX-Tg小鼠的发病率高得多。gp 130（F759/F759）小鼠的症状，包括淋巴结病，脾肿大，高γ球蛋白血症，自身抗体产生，外周淋巴器官中记忆/活化T细胞和粒细胞增加，以及II类MHCbright CD 11 c（+）群体减少，在双突变体中增加。在三重突变体IL-6（-/-）/gp 130（F759/F759）/pX-Tg中观察到发病率、严重程度和免疫学异常的显著降低，表明双突变体中的关节炎是IL-6依赖性的。gp 130（F759/F759）/pX-Tg是一种独特的RA小鼠模型。
Rheumatoid arthritis (RA) is a polygenic autoimmune disease. The autoimmunity develops from synergistic actions of genetic and environmental factors. We generated a double-mutant mouse by crossing two murine models of RA, a gp130 mutant knock-in mouse (gp130(F759/F759)) and an HTLV-1 pX transgenic mouse (pX-Tg), in a C57BL/6 background, which is resistant to arthritis. The mice spontaneously developed severe arthritis with a much earlier onset than the gp130(F759/F759) mice and with a much higher incidence than did the pX-Tg mice. The symptoms of gp130(F759/F759) mice, including lymphoadenopathy, splenomegaly, hyper-gamma-globulinemia, autoantibody production, increases in memory/activated T cells and granulocytes in the peripheral lymphoid organs, and a decrease in the class II MHCbright CD11c(+) population, were augmented in the double mutants. Marked reductions in incidence, severity and immunological abnormalities were seen in the triple mutant, IL-6(-/-)/gp130(F759/F759)/pX-Tg, indicating that the arthritis in the double mutant is IL-6 dependent. gp130(F759/F759)/pX-Tg is a unique mouse model for RA.