FOXP3 controls regulatory T cell function through cooperation with NFAT - PubMed (original) (raw)

Comparative Study

. 2006 Jul 28;126(2):375-87.

doi: 10.1016/j.cell.2006.05.042.

Madhuri Borde, Vigo Heissmeyer, Markus Feuerer, Ariya D Lapan, James C Stroud, Darren L Bates, Liang Guo, Aidong Han, Steven F Ziegler, Diane Mathis, Christophe Benoist, Lin Chen, Anjana Rao

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Comparative Study

FOXP3 controls regulatory T cell function through cooperation with NFAT

Yongqing Wu et al. Cell. 2006.

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Abstract

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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