Foxp3 occupancy and regulation of key target genes during T-cell stimulation

Alexander Marson, Karsten Kretschmer, Garrett M. Frampton, Elizabeth S. Jacobsen, Julia K. Polansky, Kenzie D. MacIsaac, Stuart S. Levine, Ernest Fraenkel, Harald von Boehmer () and Richard A. Young ()
Additional contact information
Alexander Marson: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Karsten Kretschmer: Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
Garrett M. Frampton: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Elizabeth S. Jacobsen: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Julia K. Polansky: Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
Kenzie D. MacIsaac: Department of Electrical Engineering and Computer Science,
Stuart S. Levine: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Ernest Fraenkel: Biological Engineering Division,
Harald von Boehmer: Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
Richard A. Young: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA

Nature, 2007, vol. 445, issue 7130, 931-935

Abstract: Abstract Foxp3+CD4+CD25+ regulatory T (Treg) cells are essential for the prevention of autoimmunity1,2. Treg cells have an attenuated cytokine response to T-cell receptor stimulation, and can suppress the proliferation and effector function of neighbouring T cells3,4. The forkhead transcription factor Foxp3 (forkhead box P3) is selectively expressed in Treg cells, is required for Treg development and function, and is sufficient to induce a Treg phenotype in conventional CD4+CD25- T cells5,6,7,8. Mutations in Foxp3 cause severe, multi-organ autoimmunity in both human and mouse9,10,11. FOXP3 can cooperate in a DNA-binding complex with NFAT (nuclear factor of activated T cells) to regulate the transcription of several known target genes12. However, the global set of genes regulated directly by Foxp3 is not known and consequently, how this transcription factor controls the gene expression programme for Treg function is not understood. Here we identify Foxp3 target genes and report that many of these are key modulators of T-cell activation and function. Remarkably, the predominant, although not exclusive, effect of Foxp3 occupancy is to suppress the activation of target genes on T-cell stimulation. Foxp3 suppression of its targets appears to be crucial for the normal function of Treg cells, because overactive variants of some target genes are known to be associated with autoimmune disease.

Date: 2007
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature05478 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:445:y:2007:i:7130:d:10.1038_nature05478

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature05478

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().