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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2340-2352. Prepublished online as a Blood First Edition Paper on July 10, 2008; DOI 10.1182/blood-2008-01-133967. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-133967v1 112/6/2340    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 Koenen, H. J. P. M. Articles by Joosten, I. Search for Related Content PubMed PubMed Citation Articles by Koenen, H. J. P. M. Articles by Joosten, I. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human CD25highFoxp3pos regulatory T cells differentiate into IL-17–producing cells Hans J. P. M. Koenen1, Ruben L. Smeets2, Paul M. Vink2, Esther van Rijssen1, Annemieke M. H. Boots2, and Irma Joosten1 1 Department of Blood Transfusion and Transplantation Immunology, Radboud University Nijmegen Medical Centre, Nijmegen; and 2 Department of Pharmacology, NV Organon, Oss, The Netherlands The effector T-cell lineage shows great plasticity. Th17 cells are acknowledged to be instrumental in the response against microbial infection, but are also associated with autoimmune inflammatory processes. Here, we report that human regulatory T cells (CD4posCD25highFoxp3posCD127negCD27pos) can differentiate into IL-17–producing cells, when stimulated by allogeneic antigen-presenting cells, especially monocytes, in the presence of rhIL-2/rhIL-15. These regulatory T cell (Treg)–derived IL-17–producing cells showed high expression of the Th17-related transcription factor RORt and were positively identified by CCR6 expression. This differentiation process was enhanced by exogenous IL-1β, IL-23, and IL-21, whereas IL-6 or TGFβ did not affect the emergence of IL-17–producing cells. The addition of IL-1 receptor antagonist (IL-1Ra), but not anti–IL-23 antibody, reduced IL-17–producing cell numbers. When an histone deacetylase (HDAC) inhibitor trichostatin A (TSA) was evaluated, we found a profound negative effect on the emergence of IL-17–producing cells from Tregs, implying that Treg differentiation into IL-17–producing cells depends on histone/protein deacetylase activity. Thus, the data suggest that epigenetic modification underlies the phenomenon of Treg plasticity here described. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Fletcher, R. 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