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

Dipayan Rudra; Takeshi Egawa; Mark M.W. Chong; Piper Treuting; Dan R. Littman; Alexander Y. Rudensky

doi:10.1038/ni.1795

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

Dipayan Rudra, Takeshi Egawa, Mark M.W. Chong, Piper Treuting, Dan R. Littman, Alexander Y. Rudensky

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

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.

Original language	English
Pages (from-to)	1170-1177
Number of pages	8
Journal	Nature immunology
Volume	10
Issue number	11
DOIs	https://doi.org/10.1038/ni.1795
State	Published - Nov 2009

Access to Document

10.1038/ni.1795

Cite this

@article{d65999718b674d959b470c9f87faa005,

title = "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.",

author = "Dipayan Rudra and Takeshi Egawa and Chong, {Mark M.W.} and Piper Treuting and Littman, {Dan R.} and Rudensky, {Alexander Y.}",

year = "2009",

month = nov,

doi = "10.1038/ni.1795",

language = "English",

volume = "10",

pages = "1170--1177",

journal = "Nature Immunology",

issn = "1529-2908",

number = "11",

}

TY - JOUR

T1 - Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells.

AU - Rudra, Dipayan

AU - Egawa, Takeshi

AU - Chong, Mark M.W.

AU - Treuting, Piper

AU - Littman, Dan R.

AU - Rudensky, Alexander Y.

PY - 2009/11

Y1 - 2009/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=70350451993&partnerID=8YFLogxK

U2 - 10.1038/ni.1795

DO - 10.1038/ni.1795

M3 - Article

C2 - 19767756

AN - SCOPUS:70350451993

SN - 1529-2908

VL - 10

SP - 1170

EP - 1177

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this