Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice.
Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice.
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DOI：
10.4049/jimmunol.1201621
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Song WC
中科院分区：
文献类型：
--
作者：
Miwa T;Zhou L;Maldonado MA;Madaio MP;Eisenberg RA;Song WC
CD59是一种糖基磷脂酰肌醇(GPI)锚定的补体膜调节剂，表达于血细胞和外周组织。它通过抑制膜攻击复合体的形成来保护宿主细胞免受补体损伤。最近在小鼠身上的研究也表明CD59在T细胞免疫反应中的作用是机械地独立于补体的。本研究探讨CD59在小鼠狼疮MRL/LPR模型中的作用。我们将CD59a基因敲除(CD59a−/−)小鼠回交到mrl/lpr背景上，并比较了cd59a+/+-mrl/lpr和cd59a−/−-mrl/lpr在系统性自身免疫发展中的作用。我们发现CD59a缺乏显著加重了MRL/LPR小鼠的皮肤病和淋巴增殖特性。它还增加了雄性MRL/LPR小鼠的自身抗体效价，并导致更高水平的蛋白尿。骨髓移植实验表明，CD59a在骨髓来源的细胞和外周组织上的表达对淋巴细胞增殖起作用，而皮肤病的表型主要由局部CD59a的表达决定。重要的是，在CD59a−/−-mrl/lpr小鼠中，C3基因缺失或C5中和封闭单抗并不能挽救与CD59a缺乏相关的前自身免疫表型。这些结果提示CD59a通过补体非依赖性机制抑制MRL/LPR小鼠的系统自身免疫。
CD59 is a glycosylphosphatidylinositol (GPI)-anchored membrane regulator of complement expressed on blood cells as well as peripheral tissues. It protects host cells from complement injury by inhibiting formation of the membrane attack complex. Recent studies in mice have suggested also a role of CD59 in T cell immune response that was mechanistically independent of complement. In the present study, we investigated the function of CD59 in the MRL/lpr model of murine lupus. We backcrossed the Cd59a knockout (Cd59a−/−) mouse onto the MRL/lpr background and compared Cd59a+/+-MRL/lpr and Cd59a−/−-MRL/lpr littermates for the development of systemic autoimmunity. We found that CD59a deficiency significantly exacerbated the skin disease and lymphoproliferation characteristic of MRL/lpr mice. It also increased autoantibody titers and caused a higher level of proteinuria in male MRL/lpr mice. Bone marrow transfer experiments indicated that CD59a expression on both BM-derived cells and peripheral tissues played a role in lymphoproliferation, whereas the skin disease phenotype is determined mainly by local CD59a expression. Importantly, C3 gene deletion or C5 neutralization with a blocking mAb in Cd59a−/−-MRL/lpr mice did not rescue the pro-autoimmune phenotype associated with CD59a deficiency. These results together suggest that CD59a inhibits systemic autoimmunity in MRL/lpr mice through a complement-independent mechanism.
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影响因子：
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通讯作者：
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DOI：
10.1084/jem.20040863
发表时间：
2005-02-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu J;Miwa T;Hilliard B;Chen Y;Lambris JD;Wells AD;Song WC
通讯作者：
Song WC
DOI：
10.1084/jem.192.9.1339
发表时间：
2000-11-06
期刊：
The Journal of experimental medicine
影响因子：
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