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转录抑制因子Blimp-1调节T细胞稳态和功能。

Transcriptional repressor Blimp-1 regulates T cell homeostasis and function.

作者信息

Martins Gislâine A, Cimmino Luisa, Shapiro-Shelef Miriam, Szabolcs Matthias, Herron Alan, Magnusdottir Erna, Calame Kathryn

机构信息

Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

出版信息

Nat Immunol. 2006 May;7(5):457-65. doi: 10.1038/ni1320. Epub 2006 Mar 26.

Abstract

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.

摘要

B淋巴细胞诱导成熟蛋白1(Blimp-1)转录抑制因子是B淋巴细胞终末分化所必需的。在此,我们证明了Blimp-1在T细胞谱系中的功能。缺乏Blimp-1的胸腺细胞存活率降低,且缺乏Blimp-1的小鼠外周效应T细胞更多。缺乏Blimp-1的小鼠早在6周龄时就出现了严重的结肠炎,且缺乏Blimp-1的调节性T细胞在阻断结肠炎发展方面存在缺陷。T细胞受体刺激后,Blimp-1 mRNA表达显著增加。与野生型CD4(+) T细胞相比,缺乏Blimp-1的CD4(+) T细胞在T细胞受体刺激后增殖更多,产生过量的白细胞介素2和干扰素-γ,但白细胞介素10减少。这些结果强调了Blimp-1在控制T细胞稳态和激活方面的关键作用。

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