Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis.
Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis.
复制标题
多发性硬化症患者的外周血T淋巴细胞中的KV1.3通道上调。
DOI：
10.3389/fphar.2021.714841
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Poulopoulou C
中科院分区：
文献类型：
--
作者：
Markakis I;Charitakis I;Beeton C;Galani M;Repousi E;Aggeloglou S;Sfikakis PP;Pennington MW;Chandy KG;Poulopoulou C
电压门控Kv1.3钾通道是T淋巴细胞活化、增殖和细胞因子产生的关键调节剂，通过为免疫刺激后的钙内流提供必要的膜超极化。值得注意的是，体内和体外证据的积累将这些通道与多发性硬化症的病理生理学联系起来。在这里，我们研究了电生理特性和T淋巴细胞Kv1.3通道的转录和翻译表达在多发性硬化症，结合膜片钳记录，逆转录聚合酶链反应和流式细胞术新鲜分离的外周血T淋巴细胞从两个患者队列多发性硬化症，以及从健康和疾病对照。我们的数据表明，与对照组相比，MS中的T淋巴细胞表现出Kv1.3 mRNA、Kv1.3膜蛋白和Kv1.3电流密度以及功能性膜通道蛋白的显著上调（p < 0.001）。有趣的是，患者亚组显示，与复发缓解型多发性硬化症相比，继发进展型多发性硬化症的Kv1.3通道密度显著更高（p < 0.001）。考虑到Kv1.3通道活性和钙依赖性过程之间的紧密联系，我们的数据预测并可以部分解释报道的多发性硬化症T淋巴细胞功能的改变，同时强调Kv1.3通道是该疾病的潜在治疗靶点和外周生物标志物。
Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease.
登录
查看更多内容
影响因子：
16.6
作者：
Chiang EY;Li T;Jeet S;Peng I;Zhang J;Lee WP;DeVoss J;Caplazi P;Chen J;Warming S;Hackos DH;Mukund S;Koth CM;Grogan JL
通讯作者：
Grogan JL
影响因子：
9.9
作者：
Lublin FD;Reingold SC;Cohen JA;Cutter GR;Sørensen PS;Thompson AJ;Wolinsky JS;Balcer LJ;Banwell B;Barkhof F;Bebo B Jr;Calabresi PA;Clanet M;Comi G;Fox RJ;Freedman MS;Goodman AD;Inglese M;Kappos L;Kieseier BC;Lincoln JA;Lubetzki C;Miller AE;Montalban X;O'Connor PW;Petkau J;Pozzilli C;Rudick RA;Sormani MP;Stüve O;Waubant E;Polman CH
通讯作者：
Polman CH
影响因子：
9.9
作者：
Comi, C;Leone, M;Dianzani, U
通讯作者：
Dianzani, U
影响因子：
4.8
作者：
Beeton, C;Wulff, H;Chandy, KG
通讯作者：
Chandy, KG
影响因子：
8.7
作者：
Gourraud PA;Harbo HF;Hauser SL;Baranzini SE
通讯作者：
Baranzini SE