Transcriptional mechanisms underlying lymphocyte tolerance
Transcriptional mechanisms underlying lymphocyte tolerance
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DOI：
10.1016/s0092-8674(02)00767-5
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发表时间：
2002-06-14
期刊：
影响因子：
64.5
通讯作者：
Rao, A
中科院分区：
文献类型：
--
作者：
Macián, F;García-Cózar, F;Rao, A
在淋巴细胞中，Call和其他信号传导途径的整合导致生产性激活，而未对抗的Call信号传导导致耐受性或无反应性。我们发现，钙调节转录因子NFAT在淋巴细胞功能的两个方面都有不可或缺的作用。Ca 2 +/钙调神经磷酸酶信号传导诱导有限的一组无能量相关基因，与产生性免疫反应中诱导的基因不同;这些基因在耐受性T细胞中体内上调，并且在很大程度上依赖于NFAT。缺乏NFAT 1的T细胞对无反应性诱导具有抗性;相反，如果阻止NFAT 1与其转录伴侣AP-1（Fos/Jun）相互作用，则NFAT 1诱导T细胞无反应性。因此，在AP-1的情况下，NFAT施加淋巴细胞无反应性的遗传程序，其对抗由合作NFAT：AP-1复合物介导的生产性激活程序。
In lymphocytes, integration of Call and other signaling pathways results in productive activation, while unopposed Call signaling leads to tolerance or anergy. We show that the Ca2+-regulated transcription factor NFAT has an integral role in both aspects of lymphocyte function. Ca2+/calcineurin signaling induces a limited set of anergy-associated genes, distinct from genes induced in the productive immune response; these genes are upregulated in vivo in tolerant T cells and are largely NFAT dependent. T cells lacking NFAT1 are resistant to anergy induction; conversely, NFAT1 induces T cell anergy if prevented from interacting with its transcriptional partner AP-1 (Fos/Jun). Thus, in the absence of AP-1, NFAT imposes a genetic program of lymphocyte anergy that counters the program of productive activation mediated by the cooperative NFAT:AP-1 complex.