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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4368-4375. Prepublished online as a Blood First Edition Paper on January 16, 2007; DOI 10.1182/blood-2006-11-055756. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-11-055756v1 109/10/4368    most recent Alert me when this article is cited Alert me if a correction is posted 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 Yao, Z. Articles by O'Shea, J. J Search for Related Content PubMed PubMed Citation Articles by Yao, Z. Articles by O'Shea, J. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 2, 2006 Accepted January 8, 2007 Nonredundant roles for Stat5a/b in directly regulating Foxp3 Zhengju Yao, Yuka Kanno, Marc Kerenyi, Geoffrey Stephens, Lydia Durant, Wendy T Watford, Arian Laurence, Gertraud W. Robinson, Ethan M Shevach, Richard Morrigl, Lothar Hennighausen, Changyou Wu, and John J O'Shea* Molecular Immunology and Inflammation Branch, NIAMS/NIH, Bethesda, MD, United States Dept of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna (MUW), Vienna, Austria Laboratory of Immunology, NIAID/NIH, Bethesda, MD, United States Laboratory of Genetics and Physiology, NIDDK, NIH, Bethesda, MD, United States Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria Department of Immunology, Zhongshan Medical School, Sun Yat-sen University, China * Corresponding author; email: osheajo{at}mail.nih.gov. Stats (signal transducers and activators of transcription) regulate multiple aspects of T cell fate. T regulatory (Treg) cells are a critical subset that limits immune responses, but the relative importance of Stat5a/b versus Stat3 for Treg cell development has been contentious. We observed that peripheral CD25+CD4+ T cells were reduced in Stat5N mice; however, the levels of Foxp3, a transcription factor that is critical for Treg cells, were normal in splenic CD4+ T cells even though they were reduced in the thymus. In contrast, complete deletion of Stat5a/b (Stat5-/-) resulted in dramatic reduction in CD25- or Foxp3-expressing CD4+ T cells. An intrinsic requirement was demonstrated by reduction of Stat5a/b in CD4-expressing cells and by stem cell transplantation using Stat5-/- fetal liver cells. Stat5a/b were also required for optimal induction of Foxp3 in vitro and bound directly to the foxp3 gene. Reduction of Stat3 in T cells did not reduce the numbers of Treg cells in the thymus or spleen; however, Stat3 was required for IL-6-dependent down-regulation of Foxp3. Therefore, we conclude that Stat5a/b have an essential, non-redundant role in regulating Treg cells and that Stat3 and Stat5a/b appear to have opposing roles in the regulation of Foxp3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Chen, L. Fang, S. Song, T. B. Guo, A. Liu, and J. Z. Zhang Thymic Regulation of Autoimmune Disease by Accelerated Differentiation of Foxp3+ Regulatory T Cells through IL-7 Signaling Pathway J. Immunol., November 15, 2009; 183(10): 6135 - 6144. [Abstract] [Full Text] [PDF] S. Sakaguchi, K. Wing, Y. Onishi, P. Prieto-Martin, and T. Yamaguchi Regulatory T cells: how do they suppress immune responses? Int. Immunol., October 1, 2009; 21(10): 1105 - 1111. [Abstract] [Full Text] [PDF] M. Shi, T. H. Lin, K. C. 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