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The regulation of protective immunity to viruses by L-selectin

L-选择素对病毒保护性免疫的调节

基本信息

批准号：
BB/S002480/1
负责人：
Ann Ager
金额：
$ 71.09万
依托单位：
CARDIFF UNIVERSITY
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FS002480%2F1
关键词：
regulation protective immunity viruses selectin

项目摘要

Virus infections in animals and humans cause morbid and fatal diseases which incur a severe economic burden. The ability of animals and humans to combat viruses depends on a subset of white blood cells called T lymphocytes. When a virus enters the body, T lymphocytes are presented with virus extracts in local lymph glands and turned into killer T cells before they are despatched to fight the virus. Some killer T cells turn into memory T cells which remember the virus and prevent re-infection. How killer T cells find their way to virus infected tissues, such as influenza infected lungs, is not understood.Our latest work has identified a homing molecule on killer T cells, called L-selectin, that directs them to virus-infected tissues and maintains immune memory to that virus. L-selectin is lost from the surface of T lymphocytes as they turn into killer T cells. So more of it needs to be made by the killer T-cells before they leave the lymph glands, otherwise they can't sense detect infected cells in the body. By increasing the expression of L-selectin on killer T cells we can increase the number of killer T cells at the site of infection and boost killing of virus. However, if T lymphocytes do not make more L-selectin they are unable to locate where virus is growing and clear it from the bodyIn this proposal we want to find out how the level of L-selectin on the surface of killer T cells is controlled and what effect L-selectin has on memory T cells. We will also identify how L-selectin senses a virus-infected tissue by finding what binds to it to make T-lymphocytes go to the virus infected organs. There are currently no anti-viral drugs for many of the viruses that cause significant morbidity in animals and mortality in young and elderly humans. Furthermore, vaccines are either not available or need to be re-formulated every season, like with influenza. Our studies of killer T cell homing have revealed a new way of boosting the immune system. This is by increasing the homing of killer T cells to virus infected tissues. Understanding how L-selectin is involved in killer T cells will help to develop new approaches to combat viral infections in people and livestock.

在动物和人类中感染病毒会导致病态和致命的疾病，从而造成严重的经济负担。动物和人类对抗病毒的能力取决于一种名为T淋巴细胞的白细胞亚群。当病毒进入人体时，T淋巴细胞在局部淋巴腺中被呈递病毒提取物，并在被送往对抗病毒之前转化为杀伤T细胞。一些杀手T细胞转化为记忆T细胞，记忆病毒并防止再次感染。杀手T细胞如何进入病毒感染的组织，如流感感染的肺部，目前还不清楚。我们最新的工作发现了杀手T细胞上的一个归巢分子，称为L-选择素，它引导它们进入病毒感染的组织，并维持对病毒的免疫记忆。L-选择素在T淋巴细胞转化为杀伤T细胞的过程中从表面消失。因此，在杀手T细胞离开淋巴腺之前，它们需要制造更多的这种物质，否则它们无法感觉到体内被感染的细胞。通过增加杀伤T细胞上L-选择素的表达，可以增加感染部位的杀伤T细胞的数量，促进病毒的杀伤。然而，如果T淋巴细胞不产生更多的L-选择素，它们就无法定位病毒生长的位置并将其从体内清除。在这项建议中，我们想要了解杀伤性T细胞表面L-选择素的水平是如何控制的，以及L-选择素对记忆T细胞有什么影响。我们还将通过发现什么与病毒感染组织结合，使T淋巴细胞进入病毒感染的器官，来确定L-选择素是如何感知病毒感染的组织的。目前还没有针对许多病毒的抗病毒药物，这些病毒在动物中造成重大发病率，并在年轻人和老年人中造成死亡。此外，疫苗要么不可用，要么需要每个季节重新配制，就像流感一样。我们对杀手T细胞归巢的研究揭示了一种增强免疫系统的新方法。这是通过增加杀手T细胞对病毒感染组织的归宿来实现的。了解L-选择素是如何参与杀伤T细胞的，将有助于开发新的方法来抗击人和牲畜的病毒感染。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.

DOI：
10.3390/pathogens11020150
发表时间：
2022-01-25
期刊：
Pathogens (Basel, Switzerland)
影响因子：
0
作者：
Reed SG;Ager A
通讯作者：
Ager A

Primary breast tumours but not lung metastases induce protective anti-tumour immune responses after Treg-depletion.

DOI：
10.1007/s00262-020-02603-x
发表时间：
2020-10
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
0
作者：
Hughes E;Lauder SN;Smart K;Bloom A;Scott J;Jones E;Somerville M;Browne M;Blainey A;Godkin A;Ager A;Gallimore A
通讯作者：
Gallimore A

ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells.

L-选择素的 ADAM17 依赖性蛋白水解促进细胞毒性 T 细胞的早期克隆扩增。

DOI：
10.1038/s41598-019-41811-z
发表时间：
2019
期刊：
Scientific reports
影响因子：
4.6
作者：
Mohammed RN
通讯作者：
Mohammed RN

Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry.

DOI：
10.1172/jci91512
发表时间：
2018-04-02
期刊：
The Journal of clinical investigation
影响因子：
0
作者：
Miles JJ;Tan MP;Dolton G;Edwards ES;Galloway SA;Laugel B;Clement M;Makinde J;Ladell K;Matthews KK;Watkins TS;Tungatt K;Wong Y;Lee HS;Clark RJ;Pentier JM;Attaf M;Lissina A;Ager A;Gallimore A;Rizkallah PJ;Gras S;Rossjohn J;Burrows SR;Cole DK;Price DA;Sewell AK
通讯作者：
Sewell AK