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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-03-0669. This Article 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 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 Ruckert, R. Search for Related Content PubMed PubMed Citation Articles by Brandt, K. Articles by Ruckert, R. Social Bookmarking                   What's this? Submitted March 3, 2003 Accepted July 21, 2003 Interleukin-21 inhibits dendritic cell activation and maturation Katja Brandt, Silvia Bulfone-Paus, Donald C Foster, and Rene Ruckert* Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany ZymoGenetics Inc, Seattle, WA, USA * Corresponding author; email: rrueckert{at}fz-borstel.de. IL-21 is a newly described cytokine with homology to IL-4 and IL-15. They belong to a cytokine family, which use the common -chain for signaling but also have their private high-affinity receptors. Since IL-4 is well-known to modulate differentiation and activation of dendritic cells (DC), we analyzed effects of IL-21 in comparison to IL-15 on DC differentiation, maturation and function. Here we show that DCs generated with GMCSF in the presence of IL-21 (IL-21DCs) differentiated into phenotypic and functional altered DCs characterized by reduced MHCII expression, high antigen-uptake and low stimulatory capacity for T-cell activation in vitro. Additionally, IL-21DCs completely failed to induce Ag-specific, T-cell mediated contact-hypersensitivity. Furthermore, IL-21 blocked LPS induced activation and maturation of DCs, which was not mediated by release of the anti-inflammatory cytokine IL-10. In contrast, if IL-15 was supplemented to GMCSF, DCs differentiated into mature APCs with low antigen-uptake and high significantly increased capacities to stimulate T-cells in vitro and in vivo. Taken together these results identify a dichotomous action of these structural 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 therapeutical manipulation of DC-induced immune-reactions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Sondergaard, J. M. Coquet, A. P. Uldrich, N. McLaughlin, D. I. Godfrey, P. V. Sivakumar, K. Skak, and M. J. Smyth Endogenous IL-21 Restricts CD8+ T Cell Expansion and Is not Required for Tumor Immunity J. Immunol., December 1, 2009; 183(11): 7326 - 7336. [Abstract] [Full Text] [PDF] S.-H. Lee, K.-S. Kim, N. Fodil-Cornu, S. M. Vidal, and C. A. Biron Activating receptors promote NK cell expansion for maintenance, IL-10 production, and CD8 T cell regulation during viral infection J. Exp. Med., September 28, 2009; 206(10): 2235 - 2251. 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