Hedgehog signalling in gamma delta T-cell differentiation

γ δ T 细胞分化中的 Hedgehog 信号传导

• 批准号: BB/T020970/1
• 负责人: Tessa Crompton
• 金额: $ 63.2万
• 依托单位: University College London
• 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%2FT020970%2F1
• 关键词: Hedgehog; signalling; gamma; delta; cell

T-cells are white blood cells that enable us to fight infectious disease by attacking infections and also by coordinating the immune response. T-cells are produced in an organ called the thymus. The thymus is essential, as people born without a thymus have no T-cells and cannot fight infectious disease, but after adolescence the thymus becomes smaller and it makes fewer T-cells and in elderly people it does not function well. This project will investigate how a rare type of T-cells called gamma delta T-cells are produced in the thymus at different life-stages. Gamma delta T cells are unusual because during development in the foetus different types of these cells are made at different times and then these different types of cell migrate to different tissues in the body, such as skin, gut, liver and lung, where they stay throughout the life span of the individual. Gamma delta cells are important at these sites to prevent infections, but they can also become over-active and cause inflammation so it is important to understand what controls them. Gamma delta cells are also made in the thymus after birth but different kinds of gamma delta T-cells are made after birth than in the foetus. This project will investigate why the thymus makes different kinds of gamma delta T-cells at different life-stages and will investigate what kinds of gamma delta cells are made in the old thymus compared to young adult thymus. In particular, we will investigate how proteins called Shh and Gli3 control gamma delta T-cell development at different life-stages.

t细胞是一种白细胞，它使我们能够通过攻击感染和协调免疫反应来对抗传染病。t细胞产生于一个叫做胸腺的器官。胸腺是必不可少的，因为出生时没有胸腺的人没有t细胞，无法抵抗传染病，但在青春期后，胸腺变小，产生的t细胞减少，老年人的胸腺功能不佳。这个项目将研究一种叫做伽马δ t细胞的罕见t细胞是如何在不同的生命阶段在胸腺中产生的。T细胞很不寻常，因为在胎儿发育过程中不同类型的T细胞在不同的时间产生，然后这些不同类型的细胞迁移到身体的不同组织，比如皮肤，肠道，肝脏和肺部，在个体的整个生命周期中都待在那里。伽马δ细胞在这些部位对预防感染很重要，但它们也可能变得过度活跃并引起炎症，因此了解是什么控制了它们很重要。出生后胸腺也会产生伽马δ t细胞但出生后产生的伽马δ t细胞与胎儿产生的不同。该项目将研究为什么胸腺在不同的生命阶段产生不同种类的伽马δ t细胞，并将研究老年胸腺与年轻成年胸腺相比产生哪种伽马δ细胞。特别是，我们将研究Shh和Gli3蛋白如何在不同生命阶段控制γ δ t细胞的发育。

项目成果

Systemic Pharmacological Smoothened Inhibition Reduces Lung T-Cell Infiltration and Ameliorates Th2 Inflammation in a Mouse Model of Allergic Airway Disease.

• DOI: 10.3389/fimmu.2021.737245
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Yánez DC;Papaioannou E;Chawda MM;Rowell J;Ross S;Lau CI;Crompton T
• 通讯作者: Crompton T

The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease.

• DOI: 10.3389/fimmu.2022.890781
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3

Hedgehog signalling in allograft vasculopathy: a new therapeutic target?

同种异体移植血管病中的 Hedgehog 信号传导：新的治疗靶点？

• DOI: 10.1016/j.tips.2023.05.005
• 发表时间: 2023
• 期刊: Trends in pharmacological sciences
• 影响因子: 13.8
• 作者: Rowell J

Distinct T Cell Receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus

胎儿和成人胸腺之间不同的 T 细胞受体 (TCR) 基因片段使用和 MHC 限制

• DOI: 10.1101/2023.09.20.558574
• 发表时间: 2023
• 作者: Rowell J

Cryopreservation of mouse thymus depletes thymocytes but supports immune reconstitution on transplantation.

小鼠胸腺的冷冻保存会消耗胸腺细胞，但支持移植时的免疫重建。

• DOI: 10.1002/eji.202350546
• 发表时间: 2023
• 期刊: European journal of immunology
• 影响因子: 5.4
• 作者: Chawda MM