title: Ca2+ signaling through ryanodine receptor 1 enhances maturation and activation of human dendritic cells.
abstract: 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.
authors.affiliation: Institute of Surgical Research, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Bracci
authors.forename: Mirko
authors.initials: M
authors.lastname: Vukcevic
authors.forename: Giulio
authors.initials: G
authors.lastname: Spagnoli
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ducreux
authors.forename: Francesco
authors.initials: F
authors.lastname: Zorzato
authors.forename: Susan
authors.initials: S
authors.lastname: Treves
mesh_terms: D020013:Calcium Signaling / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D051193:Toll-Like Receptors