2026-06-14T03:40:30Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/177012024-11-29T14:17:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Murga, Matilde author Fernandez-Capetillo, Oscar author Field, S J author Moreno, B author Borlado, L R author Fujiwara, Y author Balomenos, D author Vicario, A author Carrera, A C author Orkin, S H author Greenberg, M E author Zubiaga, A M author 2001-12 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. Immunity . 2001 ;15(6):959-70. 10.1016/s1074-7613(01)00254-0 1074-7613 Immunity 11754817 http://hdl.handle.net/20.500.12105/17701 Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity.