Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms
Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of aut...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2015-07-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | http://www.mdpi.com/1422-0067/16/8/16880 |
id |
doaj-2fb4b51871804d1382bbccd5d10173bb |
---|---|
record_format |
Article |
spelling |
doaj-2fb4b51871804d1382bbccd5d10173bb2020-11-25T00:38:23ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-07-01168168801689610.3390/ijms160816880ijms160816880Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent MechanismsStefan Bittner0Nicole Bobak1Majella-Sophie Hofmann2Michael K. Schuhmann3Tobias Ruck4Kerstin Göbel5Wolfgang Brück6Heinz Wiendl7Sven G. Meuth8Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, GermanyLabEx ICST, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS and Université de Nice-Sophia Antipolis, Valbonne 06560, FranceDepartment of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, GermanyDepartment of Neurology, University of Würzburg, Würzburg 97070, GermanyDepartment of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, GermanyDepartment of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, GermanyDepartment of Neuropathology, University Medical Center, Georg August University, Göttingen 37073, GermanyDepartment of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, GermanyDepartment of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, GermanyLymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (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, K2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K2P5.1 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 K2P5.1 knockout (K2P5.1−/−) 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, K2P5.1−/− 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 K2P3.1 and KV1.3 seems to counterbalance the deletion of K2P5.1. 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 K2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K2P5.1-targeting drugs.http://www.mdpi.com/1422-0067/16/8/16880ion channelspotassium channelsK2P channelsK2P5.1TASK2KCNK5autoimmune neuroinflammationmultiple sclerosisEAE |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stefan Bittner Nicole Bobak Majella-Sophie Hofmann Michael K. Schuhmann Tobias Ruck Kerstin Göbel Wolfgang Brück Heinz Wiendl Sven G. Meuth |
spellingShingle |
Stefan Bittner Nicole Bobak Majella-Sophie Hofmann Michael K. Schuhmann Tobias Ruck Kerstin Göbel Wolfgang Brück Heinz Wiendl Sven G. Meuth Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms International Journal of Molecular Sciences ion channels potassium channels K2P channels K2P5.1 TASK2 KCNK5 autoimmune neuroinflammation multiple sclerosis EAE |
author_facet |
Stefan Bittner Nicole Bobak Majella-Sophie Hofmann Michael K. Schuhmann Tobias Ruck Kerstin Göbel Wolfgang Brück Heinz Wiendl Sven G. Meuth |
author_sort |
Stefan Bittner |
title |
Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms |
title_short |
Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms |
title_full |
Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms |
title_fullStr |
Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms |
title_full_unstemmed |
Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms |
title_sort |
murine k2p5.1 deficiency has no impact on autoimmune neuroinflammation due to compensatory k2p3.1- and kv1.3-dependent mechanisms |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-07-01 |
description |
Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (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, K2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K2P5.1 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 K2P5.1 knockout (K2P5.1−/−) 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, K2P5.1−/− 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 K2P3.1 and KV1.3 seems to counterbalance the deletion of K2P5.1. 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 K2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K2P5.1-targeting drugs. |
topic |
ion channels potassium channels K2P channels K2P5.1 TASK2 KCNK5 autoimmune neuroinflammation multiple sclerosis EAE |
url |
http://www.mdpi.com/1422-0067/16/8/16880 |
work_keys_str_mv |
AT stefanbittner murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT nicolebobak murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT majellasophiehofmann murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT michaelkschuhmann murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT tobiasruck murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT kerstingobel murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT wolfgangbruck murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT heinzwiendl murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms AT svengmeuth murinek2p51deficiencyhasnoimpactonautoimmuneneuroinflammationduetocompensatoryk2p31andkv13dependentmechanisms |
_version_ |
1725297593782632448 |