Defective T cell activation and autoimmune disorder in Stra13-deficient mice

被引:141
作者
Sun, H
Lu, BF
Li, RQ
Flavell, RA
Taneja, R [1 ]
机构
[1] CUNY Mt Sinai Sch Med, Dept Biochem & Mol Biol, New York, NY 10029 USA
[2] Yale Univ, Sch Med, Immunobiol Sect, Howard Hughes Med Inst, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/ni721
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Stra13, a basic helix-loop-helix transcription factor, is up-regulated upon activation of CD4(+) T cells. Here we show that Stra13-deficient mice exhibit defects in several phases of CD4(+) T cell activation. In vivo, Stra13 deficiency results in ineffective elimination of activated T and B cells, which accumulate progressively, leading to lymphoid organ hyperplasia. Consequently, aging Stra13(-/-) mice develop autoimmune disease characterized by accumulation of spontaneously activated T and B cells, circulating autoantibodies, infiltration of T and B lymphocytes in several organs and immune complex deposition in glomeruli. Our studies identify Stra13 as a key regulator of lymphocyte activation that is vital for maintenance of self-tolerance and for constraint of autoimmunity.
引用
收藏
页码:1040 / 1047
页数:8
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