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

Published online before print September 11, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0406246v1 80/6/1500    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gabriele, L. Articles by Battistini, A. Search for Related Content PubMed PubMed Citation Articles by Gabriele, L. Articles by Battistini, A.

(Journal of Leukocyte Biology. 2006;80:1500-1511.)
© 2006 by Society for Leukocyte Biology

IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features

L. Gabriele^*, A. Fragale, P. Borghi^*, P. Sestili^*, E. Stellacci, M. Venditti^*, G. Schiavoni^*, M. Sanchez^*, F. Belardelli^* and A. Battistini^,1

^* Departments of Cell Biology and Neurosciences and
Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy

¹ Correspondence: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome 00161, Italy. E-mail: battist{at}iss.it

Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1^–/–) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8⁺ subset. IRF-1^–/– splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-β, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1^–/– DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1^–/– mice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4⁺CD25⁺ regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells.

Key Words: cytokines • virus infections • tolerance • IFN regulatory factors

This article has been cited by other articles:

				A. Fragale, L. Gabriele, E. Stellacci, P. Borghi, E. Perrotti, R. Ilari, A. Lanciotti, A. L. Remoli, M. Venditti, F. Belardelli, et al. IFN Regulatory Factor-1 Negatively Regulates CD4+CD25+ Regulatory T Cell Differentiation by Repressing Foxp3 Expression J. Immunol., August 1, 2008; 181(3): 1673 - 1682. [Abstract] [Full Text] [PDF]