Role of the WNK1 pathway and osmoregulation in T cell migration and activation

WNK1 通路和渗透压调节在 T 细胞迁移和激活中的作用

• 批准号: BB/V008757/1
• 负责人: Victor Tybulewicz
• 金额: $ 180.76万
• 依托单位: The Francis Crick Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV008757%2F1
• 关键词: Role; WNK1; pathway; osmoregulation; cell

The immune system of mammals is critical for protection from infections caused by bacteria, viruses and other microorganisms. An essential part of the immune system is a white blood cell termed a T cell. T cells move around the body, travelling between different tissues via the blood system, searching for signs of infection. If they find such infections, they stop, become activated, divide rapidly and turn into specialised cells that actively fight the infection. Some T cells become killers, destroying infected cells, others become helpers that actively support the production of antibodies that are essential to clear infections. Thus, the migration and activation of T cells is a vital part of the immune response to infectious disease. We have discovered an enzyme in T cells called WNK1 which is essential for the migration and activation of T cells. Surprisingly, we have found that WNK1 controls the movement of water into the cells, which is important for the migration and activation of the T cells. We will now study how WNK1 controls this water movement and why water movement is required for T cells to migrate and become activated. We will do this by analysing the biochemical processes inside the T cells that are controlled by WNK1. Furthermore, we will discover how WNK1 contributes to immune responses, especially to infections by respiratory viruses such as influenza.

哺乳动物的免疫系统对于防止细菌、病毒和其他微生物引起的感染至关重要。免疫系统的重要组成部分是一种被称为T细胞的白细胞。T细胞在体内移动，通过血液系统在不同组织之间移动，寻找感染的迹象。如果它们发现了这样的感染，它们就会停下来，被激活，迅速分裂，变成专门的细胞，积极对抗感染。一些T细胞成为杀手，摧毁被感染的细胞，另一些则成为助手，积极支持抗体的产生，而抗体是清除感染所必需的。因此，T细胞的迁移和激活是对传染病免疫反应的重要组成部分。我们在T细胞中发现了一种叫做WNK1的酶，它对T细胞的迁移和激活至关重要。令人惊讶的是，我们发现WNK1控制水进入细胞的运动，这对T细胞的迁移和激活很重要。我们现在将研究WNK1如何控制这种水运动，以及为什么T细胞迁移和激活需要水运动。我们将通过分析由WNK1控制的T细胞内的生化过程来做到这一点。此外，我们将发现WNK1如何促进免疫反应，特别是对呼吸道病毒（如流感）的感染。

项目成果

T cell migration requires ion and water influx to regulate actin polymerization.

• DOI: 10.1038/s41467-023-43423-8
• 发表时间: 2023-12-06
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: de Boer, Leonard L.;Vanes, Lesley;Melgrati, Serena;O'May, Joshua Biggs;Hayward, Darryl;Driscoll, Paul C.;Day, Jason;Griffiths, Alexander;Magueta, Renata;Morrell, Alexander;MacRae, James I.;Kochl, Robert;Tybulewicz, Victor L. J.
• 通讯作者: Tybulewicz, Victor L. J.