Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells.
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.
Rudra
Dipayan
D
Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
Egawa
Takeshi
T
Chong
Mark M W
MM
Treuting
Piper
P
Littman
Dan R
DR
Rudensky
Alexander Y
AY
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000276:immunology; D050658:Core Binding Factor beta Subunit / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D018390:Gene Targeting; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
C493693:Cbfb protein, mouse; D050658:Core Binding Factor beta Subunit; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse