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Wu, Y.* ; Borde, M.* ; Heissmeyer, V. ; Feuerer, M.* ; Lapan, A.D.* ; Stroud, J.C.* ; Bates, D.L.* ; Guo, L.* ; Han, A.* ; Ziegler, S.F.* ; Mathis, D.* ; Benoist, C.* ; Chen, L.* ; Rao, A.*

FOXP3 controls regulatory T cell function through cooperation with NFAT.

Cell 126, 375-387 (2006)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2006
HGF-Berichtsjahr 0
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Zeitschrift Cell
Quellenangaben Band: 126, Heft: 2, Seiten: 375-387 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
Institute of Radiation Protection (ISS)
Research Unit Molecular Immune Regulation (AMIR)
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er)
Radiation Sciences
PSP-Element(e) G-551000-001
G-501100-002
PubMed ID 16873067
DOI 10.1016/j.cell.2006.05.042
WOS ID 000239552600022
Erfassungsdatum 2006-07-28
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