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Papers of the Week

Papers: 4 Nov 2023 - 10 Nov 2023

2023 Nov 05

J Autoimmun



K2.1 is a regulator of inflammatory cell responses in idiopathic inflammatory myopathies.


Nelke C, Müntefering T, Cengiz D, Theissen L, Dobelmann V, Schroeter CB, Block H, Preuße C, Michels APE, Lichtenberg S, Pawlitzki M, Pfeuffer S, Huntemann N, Zarbock A, Briese T, Kittl C, Dittmayer C, Budde T, Lundberg IE, Stenzel W, Meuth SG, Ruck T


K2.1 (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 K2.1 in the autoimmune response of IIMs. We detected K2.1 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 K2.1 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 K2.1 function also demonstrated a strong pro-inflammatory response. Conversely, these features were abrogated by activation of K2.1 and improved the disease course of a myositis mouse model. In humans, K2.1 expression was diminished in IIM patients compared to non-diseased controls arguing for the translatability of our findings. In summary, K2.1 may regulate the inflammatory response of skeletal muscle. Further research is required to understand whether K2.1 could serve as novel therapeutic target.