Ca2+ signaling through ryanodine receptor 1 enhances maturation and activation of human dendritic cells.
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.
Bracci
Laura
L
Institute of Surgical Research, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.
Vukcevic
Mirko
M
Spagnoli
Giulio
G
Ducreux
Sylvie
S
Zorzato
Francesco
F
Treves
Susan
S
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*
D019837:Ryanodine Receptor Calcium Release Channel; D051193:Toll-Like Receptors