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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2265-2274. Prepublished online as a Blood First Edition Paper on June 1, 2006; DOI 10.1182/blood-2006-02-004762. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-004762v1 108/7/2265    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 Romani, L. Articles by Puccetti, P. Search for Related Content PubMed PubMed Citation Articles by Romani, L. Articles by Puccetti, P. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Thymosin 1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance Luigina Romani, Francesco Bistoni, Katia Perruccio, Claudia Montagnoli, Roberta Gaziano, Silvia Bozza, Pierluigi Bonifazi, Giovanni Bistoni, Guido Rasi, Andrea Velardi, Francesca Fallarino, Enrico Garaci, and Paolo Puccetti From the Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy; Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy; Institute of Neurobiology and Molecular Medicine, National Council of Research (CNR), Rome, Italy; and National Institute of Health, Rome, Italy. Thymosin 1 (T1), a naturally occurring thymic peptide, primes dendritic cells (DCs) for antifungal T-helper type 1 resistance through Toll-like receptor 9 (TLR9) signaling. As TLR9 signaling also activates the immuno-suppressive pathway of tryptophan catabolism via indoleamine 2,3-dioxygenase (IDO), we examined T1 for possible induction of DC-dependent regulatory effects. T1 affected T-helper cell priming and tolerance induction by human and murine DCs and induced IDO expression and function in the latter cells. IDO activation by T1 required TLR9 and type I interferon receptor signaling and resulted in interleukin-10 production and generation of regulatory T cells. In transfer experiments, functionally distinct subsets of differentiated DCs were required for priming and tolerance to a fungal pathogen or alloantigens. In contrast, T1-primed DCs fulfilled multiple requirements, including the induction of T-helper type 1 immunity within a regulatory environment. Thus, instructive immunotherapy with T1 targeting IDO-competent DCs could allow for a balanced control of inflammation and tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Fallarino, C. Volpi, T. Zelante, C. Vacca, M. Calvitti, M. C. Fioretti, P. Puccetti, L. Romani, and U. Grohmann IDO Mediates TLR9-Driven Protection from Experimental Autoimmune Diabetes J. Immunol., November 15, 2009; 183(10): 6303 - 6312. [Abstract] [Full Text] [PDF] A. J. Hartigan, J. Westwick, G. Jarai, and C. M. Hogaboam CCR7 Deficiency on Dendritic Cells Enhances Fungal Clearance in a Murine Model of Pulmonary Invasive Aspergillosis J. Immunol., October 15, 2009; 183(8): 5171 - 5179. 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Munn, and B. R. Blazar The Indoleamine 2,3-Dioxygenase Pathway Is Essential for Human Plasmacytoid Dendritic Cell-Induced Adaptive T Regulatory Cell Generation J. Immunol., October 15, 2008; 181(8): 5396 - 5404. [Abstract] [Full Text] [PDF] A. De Luca, C. Montagnoli, T. Zelante, P. Bonifazi, S. Bozza, S. Moretti, C. D'Angelo, C. Vacca, L. Boon, F. Bistoni, et al. Functional yet Balanced Reactivity to Candida albicans Requires TRIF, MyD88, and IDO-Dependent Inhibition of Rorc J. Immunol., November 1, 2007; 179(9): 5999 - 6008. [Abstract] [Full Text] [PDF] S. Bozza, R. Gaziano, P. Bonifazi, T. Zelante, L. Pitzurra, C. Montagnoli, S. Moretti, R. Castronari, P. Sinibaldi, G. Rasi, et al. Thymosin {alpha}1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo Int. Immunol., November 1, 2007; 19(11): 1261 - 1270. [Abstract] [Full Text] [PDF] T. M. Hohl and M. 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