Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity
Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity
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DOI：
10.1016/s1074-7613(01)00254-0
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发表时间：
2001-12-01
期刊：
影响因子：
32.4
通讯作者：
Zubiaga, AM
中科院分区：
文献类型：
--
作者：
Murga, M;Fernández-Capetillo, O;Zubiaga, AM
E2 Fs是细胞增殖、分化和凋亡的重要调节因子。在这里，我们的特点E2 F2缺乏小鼠的表型。我们发现E2 F2是免疫自身耐受所必需的。E2 F2（-/-）小鼠出现迟发性自身免疫特征，其特征为广泛的炎性浸润、肾小球免疫复合物沉积和抗核抗体。E2 F2缺陷型T淋巴细胞表现出增强的TCR刺激的增殖和较低的活化阈值，导致自身反应性效应/记忆T淋巴细胞群体的积累，这似乎是引起E2 F2缺陷型小鼠自身免疫的原因。最后，我们提供了一个模型来解释E2 F2作为T淋巴细胞增殖抑制剂的意外作用的支持。而不是作为一个转录激活因子，E2 F2似乎作为一个转录抑制因子的基因所需的正常S期进入，特别是E2 F1。
E2Fs are important regulators of proliferation, differentiation, and apoptosis. Here we characterize the phenotype of mice deficient in E2F2. We show that E2F2 is required for immunologic self-tolerance. E2F2(-/-) mice develop late-onset autoimmune features, characterized by widespread inflammatory infiltrates, glomerular immunocomplex deposition, and anti-nuclear antibodies. E2F2-deficient T lymphocytes exhibit enhanced TCR-stimulated proliferation and a lower activation threshold, leading to the accumulation of a population of autoreactive effector/memory T lymphocytes, which appear to be responsible for causing autoimmunity in E2F2-deficient mice. Finally, we provide support for a model to explain E2F2's unexpected role as a suppressor of T lymphocyte proliferation. Rather than functioning as a transcriptional activator, E2F2 appears to function as a transcriptional repressor of genes required for normal S phase entry, particularly E2F1.