Murine K(2P)5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1-and K(V)1.3-Dependent Mechanisms

作者：Bittner Stefan; Bobak Nicole; Hofmann Majella Sophie; Schuhmann Michael K; Ruck Tobias; Goebel Kerstin; Brueck Wolfgang; Wiendl Heinz; Meuth Sven G

来源：International Journal of Molecular Sciences, 2015, 16(8): 16880-16896.

DOI：10.3390/ijms160816880

• ion channels
• potassium channels
• K2P channels
• K(2P)5
• 1
• TASK2
• KCNK5
• autoimmune neuroinflammation
• multiple sclerosis
• EAE

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 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.

• 出版日期2015-8