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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 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 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 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. Related Collections Signal Transduction Gene Expression Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Nonredundant roles for Stat5a/b in directly regulating Foxp3 Zhengju Yao1,2, Yuka Kanno1, Marc Kerenyi4, Geoffrey Stephens5, Lydia Durant1, Wendy T. Watford1, Arian Laurence1, Gertraud W. Robinson6, Ethan M. Shevach5, Richard Moriggl3, Lothar Hennighausen6, Changyou Wu2, and John J. O'Shea1 1 Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD; 2 Department of Immunology, Zhongshan Medical School, Sun Yat-Sen University, China; 3 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria; 4 Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna (MUW), Austria; 5 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD; 6 Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 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, nonredundant 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: A. Hosui and L. Hennighausen Genomic dissection of the cytokine-controlled STAT5 signaling network in liver Physiol Genomics, July 9, 2008; 34(2): 135 - 143. [Abstract] [Full Text] [PDF] H. Takaki, K. Ichiyama, K. Koga, T. Chinen, G. Takaesu, Y. Sugiyama, S. Kato, A. Yoshimura, and T. Kobayashi STAT6 Inhibits TGF-{beta}1-mediated Foxp3 Induction through Direct Binding to the Foxp3 Promoter, Which Is Reverted by Retinoic Acid Receptor J. Biol. Chem., May 30, 2008; 283(22): 14955 - 14962. [Abstract] [Full Text] [PDF] L. Hennighausen and G. W. Robinson Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B Genes & Dev., March 15, 2008; 22(6): 711 - 721. [Abstract] [Full Text] [PDF] J. Wang, H. Takeuchi, Y. Sonobe, S. Jin, T. Mizuno, S. Miyakawa, M. Fujiwara, Y. Nakamura, T. Kato, H. Muramatsu, et al. Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population PNAS, March 11, 2008; 105(10): 3915 - 3920. [Abstract] [Full Text] [PDF] M. Huber, V. Steinwald, A. Guralnik, A. Brustle, P. Kleemann, C. Rosenplanter, T. Decker, and M. Lohoff IL-27 inhibits the development of regulatory T cells via STAT3 Int. 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