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

Stefan Bittner³  Nicole Bobak¹  Majella-Sophie Hofmann³  Michael K. Schuhmann⁴  Tobias Ruck³  Kerstin Gl³  Wolfgang Br࿌k²  Heinz Wiendl³  Sven G. Meuth³ 

[1] LabEx ICST, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS and Université de Nice-Sophia Antipolis, Valbonne 06560, France; E-Mail:;Department of Neuropathology, University Medical Center, Georg August University, Göttingen 37073, Germany; E-Mail:;Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, Germany; E-Mails:;Department of Neurology, University of Würzburg, Würzburg 97070, Germany; E-Mail:

关键词: ion channels;    potassium channels;    K2P channels;    K_2P5.1;    TASK2;    KCNK5;    autoimmune neuroinflammation;    multiple sclerosis;    EAE;   

DOI  :  10.3390/ijms160816880

来源: mdpi

【 摘 要 】

Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K_2P5.1 (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_2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K_2P5.1 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_2P5.1 knockout (K_2P5.1^−/−) 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_2P5.1^−/− 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_2P3.1 and K_V1.3 seems to counterbalance the deletion of K_2P5.1. 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_2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K_2P5.1-targeting drugs.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.