Transcriptional repressor Blimp-1 regulates T cell homeostasis and function

被引:307
作者
Martins, GA
Cimmino, L
Shapiro-Shelef, M
Szabolcs, M
Herron, A
Magnusdottir, E
Calame, K [1 ]
机构
[1] Columbia Univ, Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Inst Human Nutr, New York, NY 10032 USA
[3] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA
[4] Columbia Univ, Coll Phys & Surg, Inst Comparat Med, New York, NY 10032 USA
[5] Columbia Univ, Coll Phys & Surg, Dept Biol Sci, New York, NY 10032 USA
[6] Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA
关键词
D O I
10.1038/ni1320
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The B lymphocyte-induced maturation protein 1 (Blimp-1) transcriptional repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4(+) T cells, Blimp-1-deficient CD4(+) T cells proliferated more and produced excess interleukin 2 and interferon-gamma but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation.
引用
收藏
页码:457 / 465
页数:9
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