Glucocorticoid‐induced TNFR‐related protein (GITR) is constitutively expressed in T regulatory (Treg) cells and regulates their suppressive function. We identified two methylated CpG islands in the Gitr locus. Using a ChIP assay, we demonstrate that both DNMT1 and methyl‐CpG‐binding domain Protein 4 (MBD4) bind to the Gitr promoter. Moreover, knockdown of DNMT1 decreases the binding activity of MBD4. We observed much higher levels of both DNMT1 and MBD4 in human CD4+CD25− conventional T (Tconv) cells. Moreover, co‐overexpression of DNMT1 and MBD4 in Treg cells significantly inhibits GITR expression and impairs their suppressive activity. Our results reveal a novel molecular mechanism by which MBD4 inhibits GITR expression in a DNMT1‐dependent manner.
Journal article
Wiley
2017-07-01T00:00:00+00:00
591
1929 - 1939
10