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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1435-1440. Prepublished online as a Blood First Edition Paper on May 9, 2006; DOI 10.1182/blood-2006-03-006403. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-006403v1 108/5/1435    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 Rutella, S. Articles by Leone, G. Search for Related Content PubMed PubMed Citation Articles by Rutella, S. Articles by Leone, G. Related Collections Perspectives Immunobiology Signal Transduction Immunotherapy Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PERSPECTIVES Tolerogenic dendritic cells: cytokine modulation comes of age Sergio Rutella, Silvio Danese, and Giuseppe Leone From the Department of Hematology, Catholic University Medical School, Rome, Italy; and the Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano, Milan, Italy. Abstract Dendritic cells (DCs) include a heterogeneous family of professional APCs involved in initiation of immunity and in immunologic tolerance. Specifically, peripheral tolerance can be achieved and maintained by promoting regulatory T-cell (Treg) responses and/or T-cell anergy or deletion. Until recently, immature developmental stages of DC differentiation were believed to induce T-cell anergy or Treg cells, whereas DCs transformed into mature DCs by activation stimuli were thought to represent immunogenic DCs capable of inciting primary T-cell responses. This paradigm has been challenged by the demonstration of Treg-cell expansion by antigen-bearing, fully mature DCs. Similarly, semimature DCs with a distinctive interleukin 10 (IL-10)+IL-12- cytokine production profile might be endowed with tolerogenic functions, supporting the concept that DC maturation per se should no longer be considered as a distinguishing feature of immunogenic as opposed to tolerogenic DCs (TDCs). Cytokine-modulated TDCs reflect an incomplete or altered status of monocyte differentiation and promote in vitro induction of Treg cells and/or in vivo protection from autoimmune diseases. Several growth factors, including IL-10, transforming growth factor (TGF-), granulocyte colony-stimulating factor (G-CSF), hepatocyte growth factor (HGF), and vasoactive intestinal peptide (VIP), modulate DC maturation and favor the differentiation of TDCs. From a therapeutic standpoint, cytokine-modulated TDCs might be beneficial for prevention and/or treatment of posttransplantation graft-versus-host disease (GVHD) and autoimmunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] R. M. Gorczynski, Z. Chen, W. He, I. Khatri, Y. Sun, K. Yu, and I. 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