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细胞是使我们能够抵抗传染病的白细胞。他们俩都可以攻击感染性病原体，并且可以组织其他类型的白细胞来攻击感染。为此，T细胞必须能够识别什么是什么？自我？什么是非自我？因此应受到攻击。 T细胞在一个称为胸腺的器官中产生。当他们成熟时，他们离开胸腺，巡逻我们的身体，寻找他们会攻击的感染。在胸腺中，选择了T细胞，以便任何可能攻击自己的T细胞（攻击？自我？）不会完成其成熟并死亡，但是能够抗击感染的T细胞被允许离开。胸腺中这种T细胞的选择对我们的健康非常重要，因为如果识别自我的T细胞？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，例如糖尿病和类风湿关节炎。该项目将研究胸腺控制哪些发育中的T细胞如何完成其​​成熟并离开胸腺，因为它们识别非自身？哪些T细胞因为认识自我而无法完成其成熟？我们将研究分子如何称呼？刺猬？胸腺制造的蛋白质控制着发育中的T细胞的命运。刺猬蛋白是由细胞制成的分子，并分泌告诉其他相邻细胞经历特定过程，例如分裂，死亡或变成其他类型的细胞。他们通过影响目标细胞中的哪些分子来做到这一点，这是由该细胞中活性的基因确定的。刺猬蛋白在我们的胚胎开发中至关重要，因为它们将信息传输到控制器官如何形成和生长的器官。我们已经表明，出生后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进行通信。他们确定胸腺中产生了多少个T细胞，可以根据发展的T细胞是否认识？自我，可以告诉开发T细胞生存，分裂或成熟？或非自我？我们旨在通过发现制造哪些分子并在刺猬蛋白信号向开发T细胞发出的时，找出刺猬蛋白给开发T细胞的信息。