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Blood, 1 December 2003, Vol. 102, No. 12, pp. 4090-4098. Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-03-0669. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0669v1 102/12/4090    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 Brandt, K. Articles by Rückert, R. Search for Related Content PubMed PubMed Citation Articles by Brandt, K. Articles by Rückert, R. Related Collections Immunobiology Phagocytes Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Interleukin-21 inhibits dendritic cell activation and maturation Katja Brandt, Silvia Bulfone-Paus, Donald C. Foster, and René Rückert From the Research Center Borstel, Department of Immunology and Cell Biology, Borstel, Germany; and ZymoGenetics Inc, Seattle, WA. Interleukin 21 (IL-21) is a newly described cytokine with homology to IL-4 and IL-15. They belong to a cytokine family that uses the common chain for signaling but also have their private high-affinity receptors. Since it is well known that IL-4 modulates differentiation and activation of dendritic cells (DCs), we analyzed effects of IL-21 compared with IL-15 on DC differentiation, maturation, and function. Here we show that DCs generated with granulocyte-macrophage colony-stimulating factor (GMCSF) in the presence of IL-21 (IL-21DCs) differentiated into phenotypically and functionally altered DCs characterized by reduced major histocompatibility complex class II (MHCII) expression, high antigen uptake, and low stimulatory capacity for T-cell activation in vitro. Additionally, IL-21DCs completely failed to induce antigen (Ag)-specific T-cell mediated contact hypersensitivity. Furthermore, IL-21 blocked lipopolysaccharide (LPS)-induced activation and maturation of DCs, which was not mediated by release of the anti-inflammatory cytokine IL-10. In contrast, when supplementing GMCSF with IL-15, DCs differentiated into mature antigen-presenting cells (APCs) with low antigen uptake and highly significant increased capacities to stimulate T cells in vitro and in vivo. Taken together, these results identify a dichotomous action of these structurally related cytokines on DCs, establishing IL-21 as inhibitory cytokine on DC activation and IL-15 as potent stimulator of DC function, making both cytokines interesting targets for therapeutic manipulation of DC-induced immune reactions. (Blood. 2003;102: 4090-4098) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G.-Y. Seo, J. Youn, and P.-H. Kim IL-21 ensures TGF-{beta}1-induced IgA isotype expression in mouse Peyer's patches J. Leukoc. Biol., May 1, 2009; 85(5): 744 - 750. [Abstract] [Full Text] [PDF] A. P.R. Sutherland, T. Van Belle, A. L. Wurster, A. Suto, M. Michaud, D. Zhang, M. J. Grusby, and M. von Herrath Interleukin-21 Is Required for the Development of Type 1 Diabetes in NOD Mice Diabetes, May 1, 2009; 58(5): 1144 - 1155. [Abstract] [Full Text] [PDF] R. Spolski, H.-P. Kim, W. Zhu, D. E. Levy, and W. J. 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