K2P2.1 is a regulator of inflammatory cell responses in idiopathic inflammatory myopathies
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
K2P2.1 (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 K2P2.1 in the autoimmune response of IIMs. We detected K2P2.1 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 K2P2.1 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 K2P2.1 function also demonstrated a strong pro-inflammatory response. Conversely, these features were abrogated by activation of K2P2.1 and improved the disease course of a myositis mouse model. In humans, K2P2.1 expression was diminished in IIM patients compared to non-diseased controls arguing for the translatability of our findings. In summary, K2P2.1 may regulate the inflammatory response of skeletal muscle. Further research is required to understand whether K2P2.1 could serve as novel therapeutic target.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:142 |
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| Enthalten in: |
Journal of autoimmunity - 142(2024) vom: 11. Jan., Seite 103136 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nelke, Christopher [VerfasserIn] |
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| Links: |
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| Themen: |
Barrier |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaut.2023.103136 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a K2P2.1 (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 K2P2.1 in the autoimmune response of IIMs. We detected K2P2.1 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 K2P2.1 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 K2P2.1 function also demonstrated a strong pro-inflammatory response. Conversely, these features were abrogated by activation of K2P2.1 and improved the disease course of a myositis mouse model. In humans, K2P2.1 expression was diminished in IIM patients compared to non-diseased controls arguing for the translatability of our findings. In summary, K2P2.1 may regulate the inflammatory response of skeletal muscle. Further research is required to understand whether K2P2.1 could serve as novel therapeutic target | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Idiopathic inflammatory myopathies | |
| 650 | 4 | |a K(2P)2.1 | |
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| 650 | 4 | |a Myovascular unit | |
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| 700 | 1 | |a Müntefering, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Cengiz, Derya |e verfasserin |4 aut | |
| 700 | 1 | |a Theissen, Lukas |e verfasserin |4 aut | |
| 700 | 1 | |a Dobelmann, Vera |e verfasserin |4 aut | |
| 700 | 1 | |a Schroeter, Christina B |e verfasserin |4 aut | |
| 700 | 1 | |a Block, Helena |e verfasserin |4 aut | |
| 700 | 1 | |a Preuße, Corinna |e verfasserin |4 aut | |
| 700 | 1 | |a Michels, Alexander P E |e verfasserin |4 aut | |
| 700 | 1 | |a Lichtenberg, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Pawlitzki, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Pfeuffer, Steffen |e verfasserin |4 aut | |
| 700 | 1 | |a Huntemann, Niklas |e verfasserin |4 aut | |
| 700 | 1 | |a Zarbock, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Briese, Thorben |e verfasserin |4 aut | |
| 700 | 1 | |a Kittl, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Dittmayer, Carsten |e verfasserin |4 aut | |
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