SEARCH:   Advanced

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: G. P. Wright, C. A. Notley, S.-A. Xue, G. M. Bendle, A. Holler, T. N. Schumacher, M. R. Ehrenstein, and H. J. Stauss Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis PNAS, November 10, 2009; 106(45): 19078 - 19083. [Abstract] [Full Text] [PDF] S. A. De Serres, M. H. Sayegh, and N. Najafian Immunosuppressive Drugs and Tregs: A Critical Evaluation! Clin. J. Am. Soc. Nephrol., October 1, 2009; 4(10): 1661 - 1669. [Abstract] [Full Text] [PDF] L. C. Chen, J. C. Delgado, P. E. Jensen, and X. Chen Direct Expansion of Human Allospecific FoxP3+CD4+ Regulatory T Cells with Allogeneic B Cells for Therapeutic Application J. Immunol., September 15, 2009; 183(6): 4094 - 4102. [Abstract] [Full Text] [PDF] J. Wang, T. W. J. Huizinga, and R. E. M. Toes De Novo Generation and Enhanced Suppression of Human CD4+CD25+ Regulatory T Cells by Retinoic Acid J. Immunol., September 15, 2009; 183(6): 4119 - 4126. [Abstract] [Full Text] [PDF] J. Zuber, A. Brodin-Sartorius, N. Lapidus, N. Patey, M. Tosolini, S. Candon, M. Rabant, R. Snanoudj, C. Panterne, E. Thervet, et al. FOXP3-enriched infiltrates associated with better outcome in renal allografts with inflamed fibrosis Nephrol. Dial. Transplant., September 3, 2009; (2009) gfp435v1. [Abstract] [Full Text] [PDF] B. OLIVITO, G. SIMONINI, S. CIULLINI, M. MORIONDO, L. BETTI, E. GAMBINERI, L. CANTARINI, M. DE MARTINO, C. AZZARI, and R. CIMAZ Th17 Transcription Factor RORC2 Is Inversely Correlated with FOXP3 Expression in the Joints of Children with Juvenile Idiopathic Arthritis J Rheumatol, September 1, 2009; 36(9): 2017 - 2024. [Abstract] [Full Text] [PDF] E. Gounaris, N. R. Blatner, K. Dennis, F. Magnusson, M. F. Gurish, T. B. Strom, P. Beckhove, F. Gounari, and K. Khazaie T-Regulatory Cells Shift from a Protective Anti-Inflammatory to a Cancer-Promoting Proinflammatory Phenotype in Polyposis Cancer Res., July 1, 2009; 69(13): 5490 - 5497. [Abstract] [Full Text] [PDF] Z.-Z. Yang, A. J. Novak, S. C. Ziesmer, T. E. Witzig, and S. M. Ansell Malignant B Cells Skew the Balance of Regulatory T Cells and TH17 Cells in B-Cell Non-Hodgkin's Lymphoma Cancer Res., July 1, 2009; 69(13): 5522 - 5530. [Abstract] [Full Text] [PDF] I. Kotsianidis, E. Nakou, I. Bouchliou, A. Tzouvelekis, E. Spanoudakis, P. Steiropoulos, I. Sotiriou, V. Aidinis, D. Margaritis, C. Tsatalas, et al. Global Impairment of CD4+CD25+FOXP3+ Regulatory T Cells in Idiopathic Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., June 15, 2009; 179(12): 1121 - 1130. [Abstract] [Full Text] [PDF] M. D. Sharma, D.-Y. Hou, Y. Liu, P. A. Koni, R. Metz, P. Chandler, A. L. Mellor, Y. He, and D. H. Munn Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes Blood, June 11, 2009; 113(24): 6102 - 6111. [Abstract] [Full Text] [PDF] K. Nistala and L. R. Wedderburn Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis Rheumatology, June 1, 2009; 48(6): 602 - 606. [Abstract] [Full Text] [PDF] M. Ayyoub, F. Deknuydt, I. Raimbaud, C. Dousset, L. Leveque, G. Bioley, and D. Valmori Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the TH17 lineage-specific transcription factor ROR{gamma}t PNAS, May 26, 2009; 106(21): 8635 - 8640. [Abstract] [Full Text] [PDF] L. Chen, E. Ahmed, T. Wang, Y. Wang, J. Ochando, A. S. Chong, and M.-L. Alegre TLR Signals Promote IL-6/IL-17-Dependent Transplant Rejection J. Immunol., May 15, 2009; 182(10): 6217 - 6225. [Abstract] [Full Text] [PDF] G. Beriou, C. M. Costantino, C. W. Ashley, L. Yang, V. K. Kuchroo, C. Baecher-Allan, and D. A. Hafler IL-17-producing human peripheral regulatory T cells retain suppressive function Blood, April 30, 2009; 113(18): 4240 - 4249. [Abstract] [Full Text] [PDF] H. G. Evans, N. J. Gullick, S. Kelly, C. Pitzalis, G. M. Lord, B. W. Kirkham, and L. S. Taams In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses PNAS, April 14, 2009; 106(15): 6232 - 6237. [Abstract] [Full Text] [PDF] L. Bugeon, L. M. Gardner, A. Rose, M. Gentle, and M. J. Dallman Cutting Edge: Notch Signaling Induces a Distinct Cytokine Profile in Dendritic Cells That Supports T Cell-Mediated Regulation and IL-2-Dependent IL-17 Production J. Immunol., December 15, 2008; 181(12): 8189 - 8193. [Abstract] [Full Text] [PDF] T. Yamazaki, X. O. Yang, Y. Chung, A. Fukunaga, R. Nurieva, B. Pappu, N. Martin-Orozco, H. S. Kang, L. Ma, A. D. Panopoulos, et al. CCR6 Regulates the Migration of Inflammatory and Regulatory T Cells J. Immunol., December 15, 2008; 181(12): 8391 - 8401. [Abstract] [Full Text] [PDF] F. Flores-Borja, E. C. Jury, C. Mauri, and M. R. Ehrenstein Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis PNAS, December 9, 2008; 105(49): 19396 - 19401. [Abstract] [Full Text] [PDF]

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