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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1584-1592. Prepublished online as a Blood First Edition Paper on October 10, 2006; DOI 10.1182/blood-2006-06-028951. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-06-028951v1 109/4/1584    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 Rodionova, E. Articles by Luft, T. Search for Related Content PubMed PubMed Citation Articles by Rodionova, E. Articles by Luft, T. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY GSK-3 mediates differentiation and activation of proinflammatory dendritic cells Elena Rodionova1,2, Michael Conzelmann1,2, Eugene Maraskovsky4, Michael Hess1,2, Michael Kirsch2, Thomas Giese3, Anthony D. Ho2, Margot Zöller5, Peter Dreger2, and Thomas Luft1,2 1 Department of Molecular Oncology/Hematology and 5 Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany; 2 Department Medicine V and 3 Institute of Immunology, University of Heidelberg, Germany; 4 CSL Limited, Melbourne, Australia The key components of the intracellular molecular network required for the expression of a specific function of dendritic cells (DCs) are as yet undefined. Using an in vitro model of human monocyte-derived DC differentiation, this study investigates the role of glycogen synthase kinase 3 (GSK-3), a multifunctional enzyme critical for cellular differentiation, apoptosis, self-renewal, and motility, in this context. We demonstrate that GSK-3 (1) inhibits macrophage development during differentiation of DCs, (2) is constitutively active in immature DCs and suppresses spontaneous maturation, and (3) acquires a proinflammatory functional status mediating high levels of IL-12, IL-6, and TNF- secretion, and partially inhibits IL-10 in the context of DC activation. In particular, GSK-3 enhances IL-12p35 mRNA expression and thus the production of the proinflammatory cytokine IL-12p70 by integrating the activities of other kinases priming GSK-3 targets and the inhibitory effects of Akt-1. GSK-3 may therefore act as a key integrator of activating and inhibitory pathways involved in proinflammatory DC differentiation and activation. 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