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

T细胞是使我们能够抗击传染病的白血球。它们都可以攻击传染性病原体本身，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？那什么是？非我？因此应该受到攻击。T细胞在一个叫做胸腺的器官中产生。当它们成熟时，它们离开胸腺，巡视我们的身体，寻找它们将攻击的感染。在胸腺中的时间里，T细胞被挑选出来，以便任何可能攻击我们自己的T细胞(攻击自己？)不会完成它们的成熟和死亡，但能够抵抗感染的T细胞可以离开。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，导致糖尿病和类风湿性关节炎等自身免疫性疾病。这个项目将研究胸腺如何控制哪些发育中的T细胞被允许完成它们的成熟并离开胸腺，因为它们识别非我？哪些T细胞不能完成他们的成熟，因为他们识别自己？我们将研究分子是如何被称为刺猬的？由胸腺产生的蛋白质控制着发育中的T细胞的命运。刺猬蛋白是由细胞制造并分泌的分子，用于告诉其他邻近细胞经历特定的过程，如分裂、死亡或转变为不同类型的细胞。它们通过影响靶细胞中制造哪些分子来做到这一点，这是由该细胞中哪些基因活跃所决定的。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，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？或者？非我？我们的目标是通过找出当Hedgehog蛋白向发育中的T细胞发出信号时，哪些分子是组成的，哪些基因变得活跃，从而找出Hedgehog蛋白质向发育中的T细胞传递什么信息。

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.