Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.
Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.
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DOI：
10.1038/ncomms14644
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发表时间：
2017-03-01
影响因子：
16.6
通讯作者：
Grogan JL
中科院分区：
文献类型：
--
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
电压门控Kv1.3和Ca2+依赖性KCa3.1是人类和大鼠T细胞表达的最普遍的K+通道。尽管在自身抗原经历的效应记忆T细胞上Kv1.3比KCa3.1优先上调，但其诱导和功能是否需要Kv1.3尚不清楚。在这里，我们显示，使用Kv1.3缺陷的大鼠，Kv1.3参与慢性激活的抗原特异性T细胞的发展。在Kv1.3敲除（KO）大鼠中，几种免疫反应是正常的，这表明KCa 3.1可以在这些特定环境下补偿Kv1.3的缺失。然而，Kv1.3 KO大鼠和Kv1.3 siRNA敲低或通道特异性抑制人T细胞的实验表明，针对自身抗原或重复破伤风类毒素刺激的最大T细胞应答需要Kv1.3和KCa 3.1。最后，我们的数据还表明，T细胞对Kv1.3或KCa3.1的依赖性可能是不可逆的抗原暴露调制。钾通道对于调节T细胞功能是必不可少的。在这里，通过表征大鼠模型和分析人类T细胞，作者确定了两种钾通道蛋白Kv1.3和KCa3.1诱导常规与自身反应性T细胞反应的差异需求。
Voltage-gated Kv1.3 and Ca2+-dependent KCa3.1 are the most prevalent K+ channels expressed by human and rat T cells. Despite the preferential upregulation of Kv1.3 over KCa3.1 on autoantigen-experienced effector memory T cells, whether Kv1.3 is required for their induction and function is unclear. Here we show, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout (KO) rats, suggesting that KCa3.1 can compensate for the absence of Kv1.3 under these specific settings. However, experiments with Kv1.3 KO rats and Kv1.3 siRNA knockdown or channel-specific inhibition of human T cells show that maximal T-cell responses against autoantigen or repeated tetanus toxoid stimulations require both Kv1.3 and KCa3.1. Finally, our data also suggest that T-cell dependency on Kv1.3 or KCa3.1 might be irreversibly modulated by antigen exposure. Potassium channels are essential for modulating T-cell functions. Here, by characterizing rat models and analysing human T cells, the authors identify differential requirements of two potassium channel proteins, Kv1.3 and KCa3.1, for the induction of conventional versus autoreactive T-cell responses.