Bedeutsamkeit der Kalziumsignale in älteren Lymphozyten
Biophysik
Immunologie
Zusammenfassung der Projektergebnisse
In the last years, we performed comprehensive assessments of the molecular repertoire governing Ca2+ signals in CD8+ T cells and investigated the influence of varying [Ca2+]ext on the main function of these cells, the lysis of target cells. Taken together, we found out that two mechanisms contribute to the overall reduction in Ca2+ signals of CD8+ T cells of elderly mice: 1) Reduced Ca2+ currents through Orai channels due to decreased expressions of STIMs and Orais. 2) A faster extrusion of Ca2+ owing to an increased expression of PMCA4. The reduced Ca2+ signals correlated with a resistance of the cytotoxic efficiency of CD8+ T cells to varying free [Ca2+]ext with age. In summary, reduced STIM/Orai expression and increased Ca2+ clearing rates following enhanced PMCA4 expression contribute to reduced Ca2+ signals in CD8+ T cells of elderly mice. These changes are apparently relevant to immune function as they reduce the Ca2+ dependency of CTL cytotoxicity. Furthermore, we observed that CD8+ T cells from elderly mice differ clearly in their killing kinetics in comparison to adult mice. The elderly CD8+ T cells revealed significantly higher target lysis after 60 and 120 min against P815 and EL4 tumor cells and may mirror different killing pathways used by CD8+ T cells. The reasons for this different killing behavior are currently part of our further investigations.
Projektbezogene Publikationen (Auswahl)
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STIM2 drives Ca2+ oscillations through store-operated Ca2+ entry caused by mild store depletion. J Physiol. 2013 Mar 15;591(Pt 6):1433-45
Thiel, Markus; Lis, Annette & Penner, Reinhold
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TRPM7 is regulated by halides through its kinase domain. Cell Mol Life Sci, 2013 Mar 8
Yu, Haijie; Zhang, Zheng; Lis, Annette; Penner, Reinhold & Fleig, Andrea
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Measuring endogenous ICRAC and ORAI currents with the patch-clamp technique. Cold Spring Harb Protoc. 2014 Jun 2;2014(6):630-7
Alansary, Dalia; Kilch, Tatiana; Holzmann, Christian; Peinelt, Christine; Hoth, Markus & Lis, Annette
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Patch-clamp measurement of ICRAC and ORAI channel activity. Cold Spring Harb Protoc. 2014 Jun 2;2014(6):602-7
Alansary, Dalia; Kilch, Tatiana; Holzmann, Christian; Peinelt, Christine; Hoth, Markus & Lis, Annette
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The minimal requirements to use calcium imaging to analyze ICRAC Cold Spring Harb Protoc. 2014 Jun 2;2014(6):638-42
Alansary, Dalia; Kilch, Tatiana; Holzmann, Christian; Peinelt, Christine; Hoth, Markus & Lis, Annette
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A calcium-redox feedback loop controls human monocyte immune responses: The role of ORAI Ca2+ channels. Sci Signal. 2016 Mar 8;9(418):ra26
Saul, Stephanie; Gibhardt, Christine S.; Schmidt, Barbara; Lis, Annette; Pasieka, Bastian; Conrad, David; Jung, Philipp; Gaupp, Rosmarie; Wonnenberg, Bodo; Diler, Ebru; Stanisz, Hedwig; Vogt, Thomas; Schwarz, Eva C.; Bischoff, Markus; Herrmann, Mathias; Tschernig, Thomas; Kappl, Reinhard; Rieger, Heiko; Niemeyer, Barbara A.; ... & Bogeski, Ivan
