Role of Wnk1 kinase in T cell adhesion and migration

Wnk1 激酶在 T 细胞粘附和迁移中的作用

• 批准号: BB/L00805X/1
• 负责人: Victor Tybulewicz
• 金额: $ 44.48万
• 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: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL00805X%2F1
• 关键词: Role; Wnk1; kinase; cell; adhesion

White blood cells are a key part of the body's immune system, playing a critical role in combating infections by viruses, bacteria and other pathogens. Our research is focussed on a type white blood cell called a T cell, which can detect the presence of an infectious agent such as a virus inside other cells. We are interested in understanding the mechanism by which a T cell recognises whether another cell contains an infectious agent within it. As part of this process, the T cell and the infected cell have to adhere tightly to each other and we are studying this process of adhesion.In recent work we have identified that a protein called Wnk1 plays an important role in regulating T cell adhesion, and in the research we are now proposing, we will extend this work by examining how the T cells function when they lack the protein, and whether this makes them defective in contributing to normal immune responses. We suspect that Wnk1 may also control how the T cells migrate through the body. Normal T cells are continuously on the move, trafficking between the blood and lymph nodes and the spleen. This continuous movement is a vital feature of the T cells as it allows them to patrol the body looking for signs of infection. We will investigate this potential function of the Wnk1 protein in controlling T cell migration.We suspect that Wnk1 functions as a signalling protein, transmitting signals from the surface of the cell to adhesion molecules. We will investigate this hypothesis further by looking for other proteins to which Wnk1 transmits a signal. Overall our aim is to understand how Wnk1 controls T cell adhesion and migration. Such knowledge will reveal new opportunities for the design of rational drugs that could modulate the function of T cells and thereby the whole immune system.

白色血细胞是人体免疫系统的关键部分，在对抗病毒、细菌和其他病原体感染方面发挥着关键作用。我们的研究集中在一种称为T细胞的白色血细胞上，它可以检测其他细胞内感染因子（如病毒）的存在。我们有兴趣了解T细胞识别另一个细胞是否含有感染因子的机制。作为这个过程的一部分，T细胞和感染细胞必须紧密粘附在一起，我们正在研究这个粘附过程。在最近的工作中，我们已经确定了一种名为Wnk 1的蛋白质在调节T细胞粘附中起着重要作用，在我们现在提出的研究中，我们将通过检查T细胞在缺乏蛋白质时的功能来扩展这项工作，以及这是否使它们在促进正常免疫反应方面有缺陷。我们怀疑Wnk 1也可能控制T细胞如何在体内迁移。正常的T细胞是不断的移动，运输之间的血液和淋巴结和脾脏。这种持续的运动是T细胞的一个重要特征，因为它允许它们在体内巡逻，寻找感染的迹象。我们将研究Wnk 1蛋白在控制T细胞迁移中的潜在功能，我们怀疑Wnk 1蛋白是一种信号蛋白，将信号从细胞表面传递给粘附分子。我们将通过寻找Wnk1传递信号的其他蛋白质来进一步研究这一假设。总的来说，我们的目标是了解Wnk 1如何控制T细胞粘附和迁移。这些知识将为设计合理的药物提供新的机会，这些药物可以调节T细胞的功能，从而调节整个免疫系统。

项目成果

Critical role of WNK1 in MYC-dependent early mouse thymocyte development.

WNK1在依赖MYC的早期小鼠胸腺细胞发育中的关键作用。

• DOI: 10.7554/elife.56934
• 发表时间: 2020-10-14
• 期刊: eLife
• 影响因子: 7.7
• 作者: Köchl R;Vanes L;Llorian Sopena M;Chakravarty P;Hartweger H;Fountain K;White A;Cowan J;Anderson G;Tybulewicz VL
• 通讯作者: Tybulewicz VL

Chloride sensing by WNK1 regulates NLRP3 inflammasome activation and pyroptosis.

• DOI: 10.1038/s41467-021-24784-4
• 发表时间: 2021-07-27
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Mayes-Hopfinger L;Enache A;Xie J;Huang CL;Köchl R;Tybulewicz VLJ;Fernandes-Alnemri T;Alnemri ES
• 通讯作者: Alnemri ES

WNK1 kinase balances T cell adhesion versus migration in vivo.

• DOI: 10.1038/ni.3495
• 发表时间: 2016-09
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Köchl R;Thelen F;Vanes L;Brazão TF;Fountain K;Xie J;Huang CL;Lyck R;Stein JV;Tybulewicz VL
• 通讯作者: Tybulewicz VL