Firmenich Laetitia, Djamgoz Mustafa B A
Department of Life Sciences, Imperial College London, London, United Kingdom.
Bioelectricity. 2020 Dec 1;2(4):418-423. doi: 10.1089/bioe.2020.0045. Epub 2020 Dec 16.
Ion channels and ionic transporters are expressed in every cell in the body, including the cells of the immune system. This international meeting was dedicated to some of the latest advances in the field and covered a range of topics in seven presentations. Zinc transport by the ZIP7 transporter expressed in the endoplasmic reticulum, transporting Zn into the cytoplasm, was shown to be essential for B-cell development and functioning. Consequently, complete loss of ZIP7 was likely to be fatal (Sophie Hambleton). The protein kinase domain of TRPM7 cation channel was involved in proinflammatory T-cell differentiation (Susanna Zierler). A particularly novel development focused on 'optogenetic immunotherapy' involving photo-switchable Ca (STIM1/ORAI) signaling in T-cells enabling spatially and temporally distinct immune signaling including transcriptional reprogramming (Yubin Zhou). Starting with genetic screening and functional genomics, T-cells were shown to express a volume-regulated anion (Cl) channel (with LRRC8C and LRRC8A as essential components). The channel's activity controlled production of inflammatory cytokines and autoimmunity in the murine spinal cord (Axel Concepcion). Ca signaling induced by CRAC/ORAI in TH17 lymphocytes in neuroinflammatory spinal cord was studied further by confocal imaging. Treg cells were found to inhibit TH17 functioning, in part, by suppressing Ca signaling. This approach could open up a novel immunotherapy method (Michael Cahalan). S1PR (a GPCR that mediates S1P signaling) and SPNS2, a lymphatic S1P transporter, controlling T-cell trafficking in lymph nodes were characterized by Susan Schwab. Finally, pathogenic/damaged cytosolic DNA binding to the cyclic GMP-AMP synthase protein to enable synthesis of the secondary messenger cyclic GMP-AMP, leading to immune response involving production of cytokines and activation of natural killer cells was demonstrated by David Raulet. Thus, the meeting highlighted how studies of cellular ion channels and ionic transporters could elucidate both the understanding of immune cell functioning and, ultimately, improve its clinical management.
离子通道和离子转运体在人体的每个细胞中都有表达,包括免疫系统的细胞。本次国际会议致力于该领域的一些最新进展,七场报告涵盖了一系列主题。内质网中表达的ZIP7转运体介导锌转运,将锌转运到细胞质中,这一过程被证明对B细胞的发育和功能至关重要。因此,ZIP7的完全缺失可能是致命的(索菲·汉布尔顿)。TRPM7阳离子通道的蛋白激酶结构域参与促炎性T细胞分化(苏珊娜·齐勒勒)。一个特别新颖的进展聚焦于“光遗传学免疫疗法”,该疗法涉及T细胞中光可切换的钙(STIM1/ORAI)信号传导,能够实现空间和时间上不同的免疫信号传导,包括转录重编程(周宇宾)。从基因筛选和功能基因组学入手,研究发现T细胞表达一种容积调节性阴离子(Cl)通道(以LRRC8C和LRRC8A为必需成分)。该通道的活性控制着小鼠脊髓中炎性细胞因子的产生和自身免疫反应(阿克塞尔·康塞普西翁)。通过共聚焦成像进一步研究了神经炎性脊髓中TH17淋巴细胞中CRAC/ORAI诱导的钙信号传导。研究发现调节性T细胞部分通过抑制钙信号传导来抑制TH17的功能。这种方法可能会开创一种新的免疫疗法(迈克尔·卡哈兰)。苏珊·施瓦布对S1PR(一种介导S1P信号传导的GPCR)和SPNS2(一种淋巴S1P转运体)进行了表征,它们控制着T细胞在淋巴结中的运输。最后,大卫·劳莱特证明了致病性/受损的胞质DNA与环GMP-AMP合酶蛋白结合,能够合成第二信使环GMP-AMP,从而引发涉及细胞因子产生和自然杀伤细胞激活的免疫反应。因此,本次会议强调了对细胞离子通道和离子转运体的研究如何既能阐明对免疫细胞功能的理解,最终又能改善其临床管理。