SEARCH:   Advanced

Blood, 1 April 2008, Vol. 111, No. 7, pp. 3599-3606. Prepublished online as a Blood First Edition Paper on January 25, 2008; DOI 10.1182/blood-2007-09-115014. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-09-115014v1 111/7/3599    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-M. Articles by Fang, D. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-M. Articles by Fang, D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY FoxP3 maintains Treg unresponsiveness by selectively inhibiting the promoter DNA-binding activity of AP-1 Sang-Myeong Lee1, Beixue Gao1, and Deyu Fang1,2 Departments of1 Otolaryngology-Head and Neck Surgery and 2 Molecular Microbiology and Immunology, University of Missouri-Columbia School of Medicine Regulatory T cells (Tregs) have been shown to play a crucial role in maintaining self-tolerance and suppressing autoimmunity. The forkhead transcription factor, FoxP3, is a key molecule necessary and sufficient for Tregs development and function. However, the molecular mechanisms by which FoxP3 regulates the phenotypic (anergic) and the functional (suppressive) characteristics of Tregs are not well defined. Here we found that the promoter DNA-binding activity of AP-1 transcription factors is selectively inhibited in the naturally occurring CD4+ CD25+ Tregs from mice. The impaired AP-1 DNA binding is not the result of the decreased nuclear translocation of AP-1 family transcription factors, including c-Jun, JunB, and c-Fos. FoxP3 significantly suppresses both the transcriptional activity and promoter DNA-binding of AP-1 by interacting with c-Jun. The N-terminus of FoxP3, but not its C-terminus forkhead domain, specifically interacts with phosphorylated c-Jun and alters c-Jun subnuclear distribution. This N-terminus of FoxP3 with nuclear localization signals (FoxP3N/NLS) is able to suppress AP-1 transcriptional activity. Ectopic expression of FoxP3N/NLS sufficiently induces the unresponsiveness of mouse primary CD4+ CD25– T cells, whereas the full-length FoxP3 is required for the suppressive functions of Tregs. These findings uncover one of the mechanisms underlying how FoxP3 maintains the unresponsiveness of Tregs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Pozo, P. Anderson, and E. Gonzalez-Rey Induction of Alloantigen-Specific Human T Regulatory Cells by Vasoactive Intestinal Peptide J. Immunol., October 1, 2009; 183(7): 4346 - 4359. [Abstract] [Full Text] [PDF] A. D. Wells New Insights into the Molecular Basis of T Cell Anergy: Anergy Factors, Avoidance Sensors, and Epigenetic Imprinting J. Immunol., June 15, 2009; 182(12): 7331 - 7341. [Abstract] [Full Text] [PDF] L.-F. Lu and A. Rudensky Molecular orchestration of differentiation and function of regulatory T cells Genes & Dev., June 1, 2009; 23(11): 1270 - 1282. [Abstract] [Full Text] [PDF] E. F. de Zoeten, I. Lee, L. Wang, C. Chen, G. Ge, A. D. Wells, W. W. Hancock, and E. Ozkaynak Foxp3 Processing by Proprotein Convertases and Control of Regulatory T Cell Function J. Biol. Chem., February 27, 2009; 284(9): 5709 - 5716. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020