HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Belladonna, M. L. Articles by Puccetti, P. Search for Related Content PubMed PubMed Citation Articles by Belladonna, M. L. Articles by Puccetti, P. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

Cutting Edge: Autocrine TGF-β Sustains Default Tolerogenesis by IDO-Competent Dendritic Cells¹

Maria L. Belladonna^2,*, Claudia Volpi^*, Roberta Bianchi^*, Carmine Vacca^*, Ciriana Orabona^*, Maria T. Pallotta^*, Louis Boon, Stefania Gizzi, Maria C. Fioretti^*, Ursula Grohmann^* and Paolo Puccetti^2,*

^* Department of Experimental Medicine and Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy; and Bioceros B.V., Utrecht, The Netherlands

CD8^– and CD8⁺ dendritic cells (DCs) are distinct subsets of mouse splenic accessory cells with opposite but flexible programs of Ag presentation, leading to immunogenic and tolerogenic responses, respectively. In this study, we show that the default tolerogenic function of CD8⁺ DCs relies on autocrine TGF-β, which sustains the activation of IDO in response to environmental stimuli. CD8^– DCs do not produce TGF-β, yet externally added TGF-β induces IDO and turns those cells from immunogenic into tolerogenic cells. The acquisition of a suppressive phenotype by CD8^– DCs correlates with activation of the PI3K/Akt and noncanonical NF-B pathways. These data are the first to link TGF-β signaling with IDO in controlling spontaneous tolerogenesis by DCs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Italian Association for Cancer Research (to P.P.).

² Address correspondence and reprint requests to Dr. Maria L. Belladonna or Dr. Paolo Puccetti, Department of Experimental Medicine, Section of Pharmacology, University of Perugia, Via del Giochetto, Perugia 06126, Italy. E-mail addresses: laurabell{at}tin.it and plopcc{at}tin.it

³ Abbreviations used in this paper: DC, dendritic cell; IKK, IB kinase; NIK, NF-B-inducing kinase; siRNA, small interfering RNA; T_reg, regulatory T cell.

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]

				F. Fallarino, G. Luca, M. Calvitti, F. Mancuso, C. Nastruzzi, M. C. Fioretti, U. Grohmann, E. Becchetti, A. Burgevin, R. Kratzer, et al. Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone J. Exp. Med., October 26, 2009; 206(11): 2511 - 2526. [Abstract] [Full Text] [PDF]

				C. Orabona, M. T. Pallotta, C. Volpi, F. Fallarino, C. Vacca, R. Bianchi, M. L. Belladonna, M. C. Fioretti, U. Grohmann, and P. Puccetti SOCS3 drives proteasomal degradation of indoleamine 2,3-dioxygenase (IDO) and antagonizes IDO-dependent tolerogenesis PNAS, December 30, 2008; 105(52): 20828 - 20833. [Abstract] [Full Text] [PDF]