Runx-CBFβ complexes control Foxp3 expression in regulatory T cells

Foxp3 plays an indispensable role in establishing stable transcriptional and functional programs of regulatory T (T(reg)) cells. Loss of Foxp3 expression in mature T(reg) cells results in a failure of suppressor function, yet the molecular mechanisms ensuring steady heritable Foxp3 expression in the Treg cell lineage remain unknown. Using T(reg) cell-specific gene targeting we found that Runx-CBFβ complexes were required for maintenance of Foxp3 mRNA and protein expression in Treg cells. Consequently, mice lacking CBFβb exclusively in the Treg cell lineage exhibited a moderate lymphproliferative syndrome. Thus, Runx-CBFβ complexes maintain stable expression of high amounts of Foxp3 and serve as an essential determinant of Treg cell lineage stability.