Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3 inducible regulatory T cells.
Sven Klunker, Mark MW Chong, Pierre-Yves Mantel, Oscar Palomares, Claudio Bassin, Mario Ziegler, Beate Rückert, Flurina Meiler, Mübeccel Akdis, Dan R Littman, Cezmi A Akdis
J Exp Med | Published : 2009
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-beta (TGF-beta) 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-beta (CBFbeta) 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 n..View full abstract
Awarded by Swiss National Science Foundation