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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 21, 2006 Accepted May 16, 2006 Thymosin alpha 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 University of Perugia CNR National Institute of Health * Corresponding author; email: lromani{at}unipg.it. Thymosin 1, a naturally occurring thymic peptide, primes dendritic cells (DCs) for antifungal T helper type 1 resistance through Toll-like receptor (TLR)9 signaling. As TLR9 signaling also activates the immunosuppressive pathway of tryptophan catabolism via indoleamine 2,3-dioxygenase (IDO), we examined T 1 for possible induction of DC-dependent regulatory effects. T 1 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 T 1 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, T 1-primed DCs fulfilled multiple requirements, including the induction of T helper type 1 immunity within a regulatory environment. Thus, instructive immunotherapy with T 1 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. [Abstract] [Full Text] [PDF] C Coquerelle, G Oldenhove, V Acolty, J Denoeud, G Vansanten, J-M Verdebout, A Mellor, J A Bluestone, and M Moser Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis Gut, October 1, 2009; 58(10): 1363 - 1373. [Abstract] [Full Text] [PDF] S. Bozza, C. Clavaud, G. Giovannini, T. Fontaine, A. Beauvais, J. Sarfati, C. D'Angelo, K. Perruccio, P. Bonifazi, S. Zagarella, et al. Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination J. Immunol., August 15, 2009; 183(4): 2407 - 2414. [Abstract] [Full Text] [PDF] A. Curti, S. Trabanelli, V. Salvestrini, M. Baccarani, and R. M. Lemoli The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology Blood, March 12, 2009; 113(11): 2394 - 2401. [Abstract] [Full Text] [PDF] W. Chen, X. Liang, A. J. Peterson, D. H. 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. Feldmesser Aspergillus fumigatus: Principles of Pathogenesis and Host Defense Eukaryot. Cell, November 1, 2007; 6(11): 1953 - 1963. [Full Text] [PDF]

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