Runx-CBFβ complexes control expression of the transcription factor Foxp3 in regulatory T cells

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Abstract
In regulatory T cells, a decrease in expression of the transcription factor Foxp3 results in loss of suppressor function. Rudensky and co-workers find that Runx-CBFβ complexes are essential for maintaining Foxp3 expression in regulatory T cells. The transcription factor Foxp3 has an indispensable role in establishing stable transcriptional and functional programs of regulatory T cells (Treg cells). Loss of Foxp3 expression in mature Treg cells results in a failure of suppressor function, yet the molecular mechanisms that ensure steady, heritable Foxp3 expression in the Treg cell lineage remain unknown. Using Treg cell–specific gene targeting, we found that complexes of the transcription factors Runx and CBFβ were required for maintenance of Foxp3 mRNA and protein expression in Treg cells. Consequently, mice lacking CBFβb exclusively in the Treg cell lineage had a moderate lymphoproliferative syndrome. Thus, Runx-CBFβ complexes maintain stable high expression of Foxp3 and serve as an essential determinant of Treg cell lineage stability.