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

T细胞是白色血细胞，使我们能够对抗传染病。它们既可以攻击传染性病原体本身，也可以组织其他类型的白色血细胞来攻击感染。要做到这一点，T细胞必须能够识别是什么？自我？什么才是非我？所以应该受到攻击。T细胞是在一个叫做胸腺的器官中产生的。当它们成熟时，它们离开胸腺，在我们的身体里巡逻，寻找它们将要攻击的感染。在胸腺中的这段时间里，T细胞被选择，以便任何可能攻击我们自己的T细胞（攻击？自我？）没有完成它们的成熟和死亡，但能够抵抗感染的T细胞被允许离开。胸腺中T细胞的这种选择对我们的健康非常重要，因为如果T细胞识别？自我？离开胸腺后，它们可能会攻击我们的身体，引起自身免疫性疾病，如糖尿病和风湿性关节炎。这个项目将研究胸腺如何控制发育中的T细胞完成成熟并离开胸腺，因为它们识别？非我？哪些T细胞没有完成它们的成熟，因为它们识别？自我？我们将研究分子如何被称为？刺猬？胸腺产生的蛋白质控制着发育中的T细胞的命运。刺猬蛋白是由细胞产生并分泌的分子，用于告诉其他相邻细胞进行特定过程，例如分裂，死亡或变成不同类型的细胞。它们通过影响靶细胞中产生的分子来做到这一点，这取决于该细胞中哪些基因是活跃的。刺猬蛋白在我们的胚胎发育中是必不可少的，因为它们将信息传递给发育中的器官，控制器官的形成和生长。我们已经证明，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不同细胞之间的通信。它们决定胸腺中产生多少T细胞，它们可以告诉发育中的T细胞生存，分裂或成熟，这取决于发育中的T细胞是否识别？自我？还是？无我？我们的目标是找出刺猬蛋白给发育中的T细胞什么信息，通过找出哪些分子被制造，哪些基因在刺猬蛋白向发育中的T细胞发出信号时变得活跃。

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.