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GSK-3 mediates differentiation and activation of proinflammatory dendritic cells

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...

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Main Authors: Rodionova, Elena (Author) , Conzelmann, Michael (Author) , Maraskovsky, Eugene (Author) , Hess, Michael (Author) , Kirsch, Michael (Author) , Giese, Thomas (Author) , Ho, Anthony Dick (Author) , Zöller, Margot (Author) , Dreger, Peter (Author) , Luft, Thomas (Author)
Format: Article (Journal)
Language:English
Published: [15 February 2007]
In: Blood
Year: 2007, Volume: 109, Issue: 4, Pages: 1584-1592
ISSN:1528-0020
DOI:10.1182/blood-2006-06-028951
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2006-06-028951
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497120420014
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Author Notes:Elena Rodionova, Michael Conzelmann, Eugene Maraskovsky, Michael Hess, Michael Kirsch, Thomas Giese, Anthony D. Ho, Margot Zöller, Peter Dreger, Thomas Luft
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Summary: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-α 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.
Item Description:Prepublished online as Blood first edition paper, October 10, 2006
Gesehen am 26.10.2021
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2006-06-028951

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