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First published online 13 June 2007
doi: 10.1242/jcs.007203
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Research Article |


1 Institute of Surgical Research, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
2 Departments of Anesthesia and Research, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
3 Department of Experimental and Diagnostic Medicine, General Pathology Section, University of Ferrara, 44100 Ferrara, Italy
Author for correspondence (e-mail: susan.treves{at}unibas.ch)
Accepted 5 May 2007
Increases in intracellular Ca2+ concentration accompany many physiological events, including maturation of dendritic cells, professional antigen-presenting cells characterized by their ability to migrate to secondary lymphoid organs where they initiate primary immune responses. The mechanism and molecules involved in the early steps of Ca2+ release in dendritic cells have not yet been defined. Here we show that the concomitant activation of ryanodine receptor-induced Ca2+ release together with the activation of Toll-like receptors by suboptimal concentrations of microbial stimuli provide synergistic signals, resulting in dendritic cell maturation and stimulation of T cell functions. Furthermore, our results show that the initial intracellular signaling cascade activated by ryanodine receptors is different from that induced by activation of Toll-like receptors. We propose that under physiological conditions, especially when low suboptimal amounts of Toll-like receptor ligands are present, ryanodine receptor-mediated events cooperate in bringing about dendritic cell maturation.
Key words: Dendritic cell, Maturation, Ryanodine receptor, Signaling
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