Defining the cellular and molecular pathogenesis of ulcerative colitis

定义溃疡性结肠炎的细胞和分子发病机制

• 批准号: G0802068/1
• 负责人: Graham Lord
• 金额: $ 149.41万
• 依托单位: King's 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=G0802068%2F1
• 关键词: Defining; cellular; molecular; pathogenesis; ulcerative

Ulcerative colitis (UC) is an incurable disease of the guts which can affect men, women and children of all ages. It can cause severe abdominal pain, bloody diarrhoea, and even cancer and many patients require surgery to help with these symptoms and complications. What is particularly worrying is that this condition is becoming more common and nobody really knows what causes it or what the best treatment is.This research aims to understand more about what causes UC and may lead to the development of new therapies.Our recent work has given us great insight in to what is likely to be going on in UC. We have found that one particular gene in cells of the immune system can upset the balance between ?good? and ?bad? bacteria in the gut and trigger inflammation in the bowel. The research showed that this gene (known as T-bet) controls the production of a key protein called TNF-alpha. Without T-bet, too much of this protein gets produced, which starts the process of inflammation in the gut. This in turn allows bacteria to cross from the gut into the body, which can aggravate the inflammation and cause ulcerative colitis. Our work is uncovering the ways in which the crucial balance between ?good? and ?bad? bacteria is maintained in the gut and what goes wrong when it is upset.UC is one type of ?autoimmune disease? that occurs when the body?s immune system makes a mistake and attacks itself. This can be triggered by the breakdown of the barrier of cells that prevents immune cells from attacking bacteria in the bowel. We?ve found that the T-bet gene is essential for maintaining the integrity of that barrier ? it?s like a peacekeeper in our guts and without it, things can get nasty.Knowing more about the events that lead to ulcerative colitis opens up several possible new ways to treat it. As well as developing drugs that affect T-bet, another approach might be to use special ?regulatory immune cells?, which have already proved effective at treating ulcerative colitis in mice.These results are very important and we hope to study these mice in a more detailed way to discover new treatments for patients with this disease, such as giving back some regulatory T cells.We aim to take these findings from the lab and turn them into new treatments to help patients as quickly as possible.

溃疡性结肠炎（UC）是一种无法治愈的肠道疾病，可影响所有年龄段的男性，女性和儿童。它可以导致严重的腹痛，出血性腹泻，甚至癌症，许多患者需要手术来帮助这些症状和并发症。特别令人担忧的是，这种情况变得越来越普遍，没有人真正知道是什么导致了它，或者最好的治疗方法是什么。这项研究旨在了解更多关于什么导致了UC，并可能导致新疗法的发展。我们最近的工作让我们对UC可能发生的事情有了很大的了解。我们已经发现，免疫系统细胞中的一种特定基因可以破坏免疫系统之间的平衡。好吗？然后呢？不好吗肠道中的细菌并引发肠道炎症。研究表明，这种基因（称为T-bet）控制着一种名为TNF-α的关键蛋白质的产生。如果没有T-bet，就会产生太多的这种蛋白质，从而启动肠道炎症过程。这反过来又允许细菌从肠道进入体内，这会加剧炎症并导致溃疡性结肠炎。我们的工作是揭示如何在关键的平衡之间？好吗？然后呢？不好吗细菌是维持在肠道和什么出错时，它是心烦意乱。UC是一种类型？自身免疫性疾病当身体？的免疫系统犯了一个错误，攻击自己。这可能是由阻止免疫细胞攻击肠道细菌的细胞屏障的破坏引发的。我们？我们？我发现T-bet基因对维持屏障的完整性至关重要？是吗？溃疡性结肠炎就像我们肠道中的一个和平卫士，如果没有它，事情会变得很糟糕。了解更多导致溃疡性结肠炎的事件，可以开辟几种可能的新方法来治疗它。调节免疫细胞？已经证明对治疗小鼠溃疡性结肠炎有效。这些结果非常重要，我们希望以更详细的方式研究这些小鼠，为患有这种疾病的患者发现新的治疗方法，例如给予一些调节性T细胞。我们的目标是从实验室获得这些发现，并将其转化为新的治疗方法，以尽快帮助患者。