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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene
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Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene

机译：在缺乏雌激素受体α基因的小鼠中自发形成脾脏生发中心的自身免疫性肾小球肾炎

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摘要

In mice, ovariectomy accelerates the progression of the end-stage renal disease glomerulosclerosis. In women, the incidence of this disease increases after menopause, and estrogen alters its progression. Polymorphisms in the human estrogen receptor ? (ERα) gene have been suggested to constitute a genetic predisposition for lupus nephritis. Here we show that by 1 year of age, mice lacking ERα (ERα~(-/-)) but not those lacking ERβ (ERβ~(-/-)) exhibit immune complex-type glomerulonephritis, proteinuria, and destruction of tubular cells with severe infiltration of B lymphocytes in the kidney and the presence of anti-DNA antibodies in serum. No gender difference occurred in the incidence or severity of these symptoms. However, in female but not in male ERα~(-/-) mice there were elevated serum levels of IgG3. Other prominent features of these mice were (ⅰ) spontaneous formation of germinal centers in the spleen in the absence of antigen challenge and (ⅱ) infiltration of plasma cells in the kidney and plasmacytosis in the spleen. Immunohistochemistry indicated a selective expression of ERα protein in the germinal centers but not in the follicular mantle zone of murine spleens and human tonsils. Our results indicate that ERα has indispensable functions in the kidney and in germinal centers, and that defective ERα signaling results in glomerulonephritis.
机译：在小鼠中，卵巢切除术可加速终末期肾脏疾病肾小球硬化的发展。在女性中，更年期后该病的发生率增加，而雌激素改变其进展。人类雌激素受体中的多态性（ERα）基因已被建议构成狼疮肾炎的遗传易感性。我们在这里显示，到1岁时，缺少ERα（ERα〜（-/-））但没有ERβ（ERβ〜（-/-））的小鼠表现出免疫复合物型肾小球肾炎，蛋白尿和肾小管细胞破坏肾中B淋巴细胞严重浸润，血清中存在抗DNA抗体。这些症状的发生率或严重性没有性别差异。然而，在雌性而不是雄性ERα〜（-/-）小鼠中，IgG3的血清水平升高。这些小鼠的其他显着特征是（ⅰ）在没有抗原攻击的情况下脾中生发中心的自发形成和（ⅱ）肾中浆细胞的浸润和脾中的浆细胞增多。免疫组织化学表明ERα蛋白在小鼠脾脏和人类扁桃体的生发中心而不是在卵泡套区中选择性表达。我们的结果表明，ERα在肾脏和生发中心具有必不可少的功能，而有缺陷的ERα信号传导会导致肾小球肾炎。

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