151. K 2P 2.1 is a regulator of inflammatory cell responses in idiopathic inflammatory myopathies.
- Author
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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, and Ruck T
- Subjects
- Humans, Animals, Mice, Muscle, Skeletal pathology, Leukocytes pathology, Endothelial Cells pathology, Myositis genetics
- 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 K2P 2.1 in the autoimmune response of IIMs. We detected K2P 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 K2P 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 K2P 2.1 function also demonstrated a strong pro-inflammatory response. Conversely, these features were abrogated by activation of K2P 2.1 and improved the disease course of a myositis mouse model. In humans, K2P 2.1 expression was diminished in IIM patients compared to non-diseased controls arguing for the translatability of our findings. In summary, K2P 2.1 may regulate the inflammatory response of skeletal muscle. Further research is required to understand whether K2P 2.1 could serve as novel therapeutic target., Competing Interests: Declaration of competing interest The authors report no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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