1. K2P2.1 is a regulator of inflammatory cell responses in idiopathic inflammatory myopathies.
- Author
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Nelke, Christopher, Müntefering, Thomas, Cengiz, Derya, Theissen, Lukas, Dobelmann, Vera, Schroeter, Christina B., Block, Helena, Preuße, Corinna, Michels, Alexander P.E., Lichtenberg, Stefanie, Pawlitzki, Marc, Pfeuffer, Steffen, Huntemann, Niklas, Zarbock, Alexander, Briese, Thorben, Kittl, Christoph, Dittmayer, Carsten, Budde, Thomas, Lundberg, Ingrid E., and Stenzel, Werner
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MYOSITIS , *INFLAMMATION , *MUSCLE diseases , *MUSCLE cells , *POTASSIUM channels , *ENDOTHELIUM diseases , *SKELETAL muscle - Abstract
K 2P 2.1 (TREK1), a two-pore domain potassium channel, has emerged as regulator of leukocyte transmigration into the central nervous system. In the context of skeletal muscle, immune cell infiltration constitutes the pathogenic hallmark of idiopathic inflammatory myopathies (IIMs). However, the underlying mechanisms remain to be elucidated. In this study, we investigated the role of K 2P 2.1 in the autoimmune response of IIMs. We detected K 2P 2.1 expression in primary skeletal muscle and endothelial cells of murine and human origin. We observed an increased pro-inflammatory cell response, adhesion and transmigration by pharmacological blockade or genetic deletion of K 2P 2.1 in vitro and in in vivo myositis mouse models. Of note, our findings were not restricted to endothelial cells as skeletal muscle cells with impaired K 2P 2.1 function also demonstrated a strong pro-inflammatory response. Conversely, these features were abrogated by activation of K 2P 2.1 and improved the disease course of a myositis mouse model. In humans, K 2P 2.1 expression was diminished in IIM patients compared to non-diseased controls arguing for the translatability of our findings. In summary, K 2P 2.1 may regulate the inflammatory response of skeletal muscle. Further research is required to understand whether K 2P 2.1 could serve as novel therapeutic target. • K 2P 2.1 (TREK1) is a potassium channel with immunoregulatory properties. • Immune cell infiltration is a pathophysiological hallmark of idiopathic inflammatory myopathies. • K 2P 2.1 regulates immune cell migration across the myovascular barrier, providing a potentially novel therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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