Nóra Legány1, Gergely Toldi2, Csaba Orbán3, Nóra Megyes1, Anna Bajnok2, Attila Balog4. 1. Department of Rheumatology, Faculty of Medicine, Albert Szent-Györgyi Health Center, University of Szeged Kálvária sgt. 57., H-6725, Szeged, Hungary. 2. First Department of Obstetrics and Gynecology, Faculty of Medicine, Semmelweis University, Budapest, Baross u. 27., H-1088, Budapest, Hungary. 3. Department of Dietetics and Nutrition Sciences, Faculty of Health Sciences, Semmelweis University, Vas u. 17., H-1088 Budapest, Hungary. 4. Department of Rheumatology, Faculty of Medicine, Albert Szent-Györgyi Health Center, University of Szeged Kálvária sgt. 57., H-6725, Szeged, Hungary. Electronic address: balog.attila@med.u-szeged.hu.
Abstract
OBJECTIVE: The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx and present a possible target for selective immunomodulation. DESIGN: Case-control study. SUBJECTS AND METHODS: We took peripheral blood samples from 8 healthy individuals and 15 primary Sjögren's syndrome (pSS) patients. We evaluated calcium influx kinetics following activation in peripheral T lymphocytes. We also assessed the sensitivity of T lymphocytes to specific inhibition of the Kv1.3 and IKCa1 potassium channels, and the Kv1.3 channel expression. RESULTS: The basal cytoplasmatic calcium levels were lower in both Th1 and Th2 lymphocytes in pSS compared to controls. The peak of calcium influx in lymphocytes isolated from pSS patients is reached later, indicating that they respond more slowly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. In the pSS group, neither of the inhibitors induced alteration in calcium influx. Expression of Kv1.3 channels on CD4, Th2 and CD8 lymphocytes in pSS was significantly higher compared to controls. CONCLUSION: The altered expression and specific inhibition of potassium channels seem to be related to altered calcium influx kinetics in pSS which distinguish pSS either from healthy controls or other systemic autoimmune diseases.
OBJECTIVE: The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx and present a possible target for selective immunomodulation. DESIGN: Case-control study. SUBJECTS AND METHODS: We took peripheral blood samples from 8 healthy individuals and 15 primary Sjögren's syndrome (pSS) patients. We evaluated calcium influx kinetics following activation in peripheral T lymphocytes. We also assessed the sensitivity of T lymphocytes to specific inhibition of the Kv1.3 and IKCa1 potassium channels, and the Kv1.3 channel expression. RESULTS: The basal cytoplasmatic calcium levels were lower in both Th1 and Th2 lymphocytes in pSS compared to controls. The peak of calcium influx in lymphocytes isolated from pSSpatients is reached later, indicating that they respond more slowly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. In the pSS group, neither of the inhibitors induced alteration in calcium influx. Expression of Kv1.3 channels on CD4, Th2 and CD8 lymphocytes in pSS was significantly higher compared to controls. CONCLUSION: The altered expression and specific inhibition of potassium channels seem to be related to altered calcium influx kinetics in pSS which distinguish pSS either from healthy controls or other systemic autoimmune diseases.
Authors: Mark R Tanner; Rajeev B Tajhya; Redwan Huq; Elizabeth J Gehrmann; Kathia E Rodarte; Mustafa A Atik; Raymond S Norton; Michael W Pennington; Christine Beeton Journal: Clin Immunol Date: 2017-04-04 Impact factor: 3.969
Authors: Sarah Y Weißenberg; Franziska Szelinski; Eva Schrezenmeier; Ana-Luisa Stefanski; Annika Wiedemann; Hector Rincon-Arevalo; Anna Welle; Annemarie Jungmann; Karl Nordström; Jörn Walter; Juliana Imgenberg-Kreuz; Gunnel Nordmark; Lars Rönnblom; Prathyusha Bachali; Michelle D Catalina; Amrie C Grammer; Peter E Lipsky; Andreia C Lino; Thomas Dörner Journal: Front Immunol Date: 2019-09-24 Impact factor: 7.561