Hedgehog signalling in T cell receptor (TCR) repertoire selection in the thymus.

胸腺 T 细胞受体 (TCR) 库选择中的 Hedgehog 信号传导。

• 批准号: G0900161/1
• 负责人: Tessa Crompton
• 金额: $ 70.01万
• 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: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900161%2F1
• 关键词: Hedgehog; signalling; cell; receptor; TCR

T-cells are white blood cells that enable us to fight infectious disease. They can both attack infectious pathogens themselves and they can organise other types of white blood cell to attack infections. To do this, T-cells must be able to recognise what is ?self? and what is ?non-self? and so should be attacked. T-cells are produced in an organ called the thymus. When they are mature they leave the thymus and patrol our bodies looking for infections that they will attack. During the time that they are in the thymus, T-cells are selected so that any T-cells that might attack ourselves (attack ?self?) do not complete their maturation and die, but T-cells that are able to fight infections are allowed to leave. This selection of T-cells in the thymus is very important to our health because if T-cells that recognise ?self? leave the thymus they might attack our bodies causing autoimmune diseases like diabetes and rheumatoid arthritis. This project will study how the thymus controls which developing T-cells are allowed to complete their maturation and leave the thymus because they recognise ?non-self? and which T-cells do not complete their maturation because they recognise ?self?. We will study how molecules called ?Hedgehog? proteins that are made by the thymus control the fate of developing T-cells. Hedgehog proteins are molecules that are made by cells and secreted to tell other neighbouring cells to undergo a particular process, such as to divide, die, or change into a different type of cell. They do this by influencing which molecules are made in the target cell, and this is determined by which genes are active in that cell. Hedgehog proteins are essential in our embryonic development because they transmit messages to developing organs controlling how the organs form and grow. We have shown that after birth Hedgehog proteins are also important in our immune systems because they allow communication between different cells of the immune system. They determine how many T-cells are produced in the thymus and they can tell developing T-cells to survive, divide, or mature, depending on if the developing T-cell recognises ?self? or ?non-self?. We aim to find out what messages Hedgehog proteins give to developing T-cells by finding out which molecules are made and which genes become active when Hedgehog proteins signal to developing T-cells.

t细胞是一种白血球，它使我们能够对抗传染病。它们既可以攻击感染性病原体本身，也可以组织其他类型的白细胞来攻击感染。要做到这一点，t细胞必须能够识别什么是自我？什么是“非我”？所以应该受到攻击。t细胞产生于一个叫做胸腺的器官。当它们成熟时，它们离开胸腺，在我们的身体里巡逻，寻找它们要攻击的感染。在胸腺中，t细胞被挑选出来，这样任何可能攻击我们自己的t细胞就不会完成它们的成熟和死亡，而那些能够抵抗感染的t细胞则被允许离开。胸腺中t细胞的选择对我们的健康非常重要，因为如果t细胞识别自我？离开胸腺，它们可能会攻击我们的身体，导致自身免疫性疾病，如糖尿病和风湿性关节炎。这个项目将研究胸腺是如何控制哪些发育中的t细胞被允许完成成熟并离开胸腺的，因为它们识别“非自我”。以及哪些t细胞因为识别“自我”而无法完成成熟。我们将学习分子是如何命名的？刺猬吗?由胸腺产生的蛋白质控制着t细胞发育的命运。刺猬蛋白是一种由细胞产生并分泌的分子，它告诉邻近的细胞经历一个特定的过程，比如分裂、死亡或转变成不同类型的细胞。它们通过影响目标细胞中产生的分子来做到这一点，而这是由该细胞中哪些基因是活跃的决定的。刺猬蛋白在我们的胚胎发育中是必不可少的，因为它们向发育中的器官传递信息，控制器官的形成和生长。我们已经证明，出生后的刺猬蛋白在我们的免疫系统中也很重要，因为它们允许免疫系统的不同细胞之间的通信。它们决定了胸腺中产生了多少t细胞，它们可以告诉发育中的t细胞存活、分裂或成熟，这取决于发育中的t细胞是否识别自我。或非自我?。我们的目标是通过发现当Hedgehog蛋白向发育中的t细胞发出信号时，哪些分子被制造出来，哪些基因变得活跃，从而发现Hedgehog蛋白给发育中的t细胞提供了什么信息。