Journal article
Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3 inducible regulatory T cells
S Klunker, MMW Chong, PY Mantel, O Palomares, C Bassin, M Ziegler, B Rückert, F Meiler, M Akdis, DR Littman, CA Akdis
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2009
DOI: 10.1084/jem.20090596
Abstract
Forkhead box P3 (FOXP3) + CD4 + CD25+ inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-β (TGF-β) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4+ T cells. This induction seems to be a prerequisite for the binding of RUNX1 and RUNX3 to three putative RUNX binding sites in the FOXP3 promoter. Inactivation of the gene encoding RUNX cofactor core-binding factor-β (CBFβ) in mice and small interfering RNA (siRNA)-mediated suppression of RUNX1 and RUNX3 in human T cells resulted in reduced expression of Foxp3. The in vivo conversion of naive CD4+T cells..
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Awarded by Swiss National Science Foundation
Funding Acknowledgements
We thank Kosei Ito, RUNX Group, Institute of Molecular and Cell Biology, Singapore for kindly providing the pCMV human RUNX3 vector. M. M. W. C is currently funded by a Helen L. and Martin S. Kimmel Center for Stem Cell Biology Fellowship, and was previously a recipient of a Cancer Research Institute Postdoctoral Fellowship. This study is sponsored by Swiss National Science Foundation grants 32125249/1 and 32-118226 and Global Allergy and Asthma European Network (GA<SUP>2</SUP>LEN), the Howard Hughes Medical Institute (D. R. Littman) and Christine Kuhne-Center for Allergy Research and Education, Davos (CK-CARE).