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Blood, 1 July 2007, Vol. 110, No. 1, pp. 211-219. Prepublished online as a Blood First Edition Paper on March 13, 2007; DOI 10.1182/blood-2006-10-052506. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-052506v1 110/1/211    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 Hamdi, H. Articles by Emilie, D. Search for Related Content PubMed PubMed Citation Articles by Hamdi, H. Articles by Emilie, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 19, 2006 Accepted March 6, 2007 Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper Haifa Hamdi, Veronique Godot, Marie-Christine Maillot, Maria Victoria Prejean, Nicolas Cohen, Roman Krzysiek, Francois Michel Lemoine, Weiping Zou, and Dominique Emilie* Institut National de la Sante et de la Recherche Medicale, U764, Clamart, France Univ Paris-Sud, Faculte de medecine Paris Sud, Institut Federatif de Recherche, Clamart, France Assistance Publique - Hopitaux de Paris, Hopital Antoine Beclere, Service de Microbiologie-Immunologie Biologique, Clamart, France CNRS-UMR 7087, Paris, and Univ Pierre et Marie Curie, Institut Federatif de Recherche 113, Paris, France Dept of Surgery, Univ of Michigan School of Medicine, Ann Arbor, MI, United States * Corresponding author; email: emilie{at}ipsc.u-psud.fr. Dendritic cells (DC) determine whether antigen presentation leads to immune activation or to tolerance. Tolerance-inducing DC (also called regulatory DC) act partly by generating regulatory T lymphocytes (Treg). The mechanism used by DC to switch towards regulatory DC during their differentiation is unclear. We show here that human DC treated in vitro with glucocorticoids produce the glucocorticoid-induced leucine zipper (GILZ). Antigen presentation by GILZ-expressing DC generates CD25highFOXP3+CTLA-4/CD152+ and interleukin-10-producing Treg inhibiting the response of CD4+ and CD8+ T lymphocytes. This inhibition is specific to the antigen presented, and only proliferating CD4+ T lymphocytes express the Treg markers. Interleukin-10 is required for Treg induction by GILZ-expressing DC. It is also needed for the suppressive function of Treg. Antigen-presenting cells from patients treated with glucocorticoids generate interleukin-10-secreting Treg ex vivo. These antigen-presenting cells produce GILZ, which is needed for Treg induction. Therefore, GILZ is critical for commitment of DC to differentiate into regulatory DC and to the generation of antigen-specific Treg. This mechanism may contribute to the therapeutic effects of glucocorticoids. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Ayroldi and C. Riccardi Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action FASEB J, November 1, 2009; 23(11): 3649 - 3658. [Abstract] [Full Text] [PDF] S. Chamorro, J. J. Garcia-Vallejo, W. W. J. Unger, R. J. Fernandes, S. C. M. Bruijns, S. Laban, B. O. Roep, B. A. 't Hart, and Y. van Kooyk TLR Triggering on Tolerogenic Dendritic Cells Results in TLR2 Up-Regulation and a Reduced Proinflammatory Immune Program J. Immunol., September 1, 2009; 183(5): 2984 - 2994. [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] C. Lagaraine, R. Lemoine, C. Baron, H. Nivet, F. Velge-Roussel, and Y. Lebranchu Induction of human CD4+ regulatory T cells by mycophenolic acid-treated dendritic cells J. Leukoc. Biol., October 1, 2008; 84(4): 1057 - 1064. [Abstract] [Full Text] [PDF] A. Dolganiuc and G. Szabo T cells with regulatory activity in hepatitis C virus infection: what we know and what we don't J. Leukoc. Biol., September 1, 2008; 84(3): 614 - 622. [Abstract] [Full Text] [PDF] K. R. Kalli, C. J. Krco, L. C. Hartmann, K. Goodman, M. J. Maurer, C. Yu, E. M. Johnson, C. L. Erskine, M. L. Disis, P. J. Wettstein, et al. An HLA-DR-Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2-Specific Immunity in Patients with Cancer Cancer Res., June 15, 2008; 68(12): 4893 - 4901. [Abstract] [Full Text] [PDF]

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