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

ABSTRACT: The transcription factor Foxp3 has an indispensable role in establishing stable transcriptional and functional programs of regulatory T cells (T(reg) cells). Loss of Foxp3 expression in mature T(reg) cells results in a failure of suppressor function, yet the molecular mechanisms that ensure steady, heritable Foxp3 expression in the T(reg) cell lineage remain unknown. Using T(reg) cell-specific gene targeting, we found that complexes of the transcription factors Runx and CBFbeta were required for maintenance of Foxp3 mRNA and protein expression in T(reg) cells. Consequently, mice lacking CBFbetab exclusively in the T(reg) cell lineage had a moderate lymphoproliferative syndrome. Thus, Runx-CBFbeta complexes maintain stable high expression of Foxp3 and serve as an essential determinant of T(reg) cell lineage stability.

SUBMITTER: Rudra D

PROVIDER: S-EPMC2764816 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Rudra Dipayan D Egawa Takeshi T Chong Mark M W MM Treuting Piper P Littman Dan R DR Rudensky Alexander Y AY

Nature immunology 20090920 11

The transcription factor Foxp3 has an indispensable role in establishing stable transcriptional and functional programs of regulatory T cells (T(reg) cells). Loss of Foxp3 expression in mature T(reg) cells results in a failure of suppressor function, yet the molecular mechanisms that ensure steady, heritable Foxp3 expression in the T(reg) cell lineage remain unknown. Using T(reg) cell-specific gene targeting, we found that complexes of the transcription factors Runx and CBFbeta were required for ...[more]

PMID: 19767756

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The evolutionary origin of the Runx/CBFbeta transcription factors--studies of the most basal metazoans.

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