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Murine K\(_{2P}\)5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K\(_{2P}\)3.1-and K\(_{V}\)1.3-Dependent Mechanisms

Please always quote using this URN: urn:nbn:de:bvb:20-opus-151454
  • Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K\(_{2P}\)5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K\(_{2P}\)5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation ofLymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K\(_{2P}\)5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K\(_{2P}\)5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K\(_{2P}\)5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K\(_{2P}\)5.1 knockout (K\(_{2P}\)5.1\(^{-/-}\) mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K\(_{2P}\)5.1\(^{-/-}\) mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K\(_{2P}\)3.1 and K\(_{V}\)1.3 seems to counterbalance the deletion of K\(_{2P}\)5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K\(_{2P}\)5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K\(_{2P}\)5.1-targeting drugs.show moreshow less

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Metadaten
Author: Stefan Bittner, Nicole Bobak, Majella-Sophie Hofmann, Michael K. Schuhmann, Tobias Ruck, Kerstin Göbel, Wolfgang Brück, Heinz Wiendl, Sven G. Meuth
URN:urn:nbn:de:bvb:20-opus-151454
Document Type:Journal article
Faculties:Medizinische Fakultät / Neurologische Klinik und Poliklinik
Language:English
Parent Title (English):International Journal of Molecular Sciences
Year of Completion:2015
Volume:16
First Page:16880
Last Page:16896
Source:International Journal of Molecular Sciences 2015, 16, 16880-16896. DOI: 10.3390/ijms160816880
DOI:https://doi.org/10.3390/ijms160816880
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:B cells; EAE; K+ channel; K2P channels; KCNK5; K\(_{2P}\)5.1; T lymphocytes; TASK2; autoimmune neuroinflammation; domain potassium channels; ion channels; multiple sclerosis; multiple-sclerosis; ph; potassium channels; up-regulation; volume regulation
Release Date:2017/10/13
EU-Project number / Contract (GA) number:026155
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International