NFAT公司
转录因子
生物
FOXP3型
细胞生物学
T细胞
白细胞介素2受体
免疫系统
遗传学
基因
作者
Yongqing Wu,Madhuri Borde,Vigo Heissmeyer,Markus Feuerer,Ariya D. Lapan,James C. Stroud,D.L. Bates,Liang Guo,Aidong Han,Steven F. Ziegler,Diane Mathis,Christophe Benoist,Lin Chen,Anjana Rao
出处
期刊:Cell
[Elsevier]
日期:2006-07-01
卷期号:126 (2): 375-387
被引量:1066
标识
DOI:10.1016/j.cell.2006.05.042
摘要
Antigen stimulation of immune cells activates the transcription factor NFAT, a key regulator of T cell activation and anergy. NFAT forms cooperative complexes with the AP-1 family of transcription factors and regulates T cell activation-associated genes. Here we show that regulatory T cell (Treg) function is mediated by an analogous cooperative complex of NFAT with the forkhead transcription factor FOXP3, a lineage specification factor for Tregs. The crystal structure of an NFAT:FOXP2:DNA complex reveals an extensive protein-protein interaction interface between NFAT and FOXP2. Structure-guided mutations of FOXP3, predicted to progressively disrupt its interaction with NFAT, interfere in a graded manner with the ability of FOXP3 to repress expression of the cytokine IL2, upregulate expression of the Treg markers CTLA4 and CD25, and confer suppressor function in a murine model of autoimmune diabetes. Thus by switching transcriptional partners, NFAT converts the acute T cell activation program into the suppressor program of Tregs.
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