Defining the cellular and molecular pathogenesis of ulcerative colitis

溃疡性结肠炎（UC）是一种无法治愈的肠道疾病，可以影响所有年龄段的男性、女性和儿童。它会导致严重的腹痛、带血腹泻，甚至癌症，许多患者需要手术来缓解这些症状和并发症。尤其令人担忧的是，这种情况变得越来越普遍，没有人真正知道是什么导致了这种情况，也没有人知道最好的治疗方法是什么。这项研究旨在了解更多导致UC的原因，并可能导致新疗法的发展。我们最近的工作让我们对加州大学可能发生的事情有了很好的了解。我们发现免疫系统细胞中的一种特殊基因可以破坏“好”与“坏”之间的平衡。和坏?肠道内的细菌会引发肠道炎症。研究表明，这种基因（被称为T-bet）控制着一种叫做tnf - α的关键蛋白质的产生。没有T-bet，就会产生过多的这种蛋白质，从而引发肠道炎症。这反过来又使细菌从肠道进入体内，从而加重炎症并引起溃疡性结肠炎。我们的工作是揭示“好”与“坏”之间的关键平衡。和坏?细菌维持在肠道中，当肠道紊乱时，什么会出问题。UC是一种？自身免疫性疾病?那发生在什么时候？人体的免疫系统犯了一个错误并攻击自己。这可能是由阻止免疫细胞攻击肠道细菌的细胞屏障破裂引起的。我们吗?我们已经发现T-bet基因对于维持屏障的完整性至关重要。它吗?就像我们的内脏里有一个维和人员，没有它，事情会变得很糟糕。更多地了解导致溃疡性结肠炎的事件，为治疗它开辟了几种可能的新方法。除了开发影响T-bet的药物外，另一种方法可能是使用特殊的？调节性免疫细胞？这种药物已被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，以发现治疗这种疾病的新方法，例如恢复一些调节性T细胞。我们的目标是将实验室的这些发现转化为新的治疗方法，以尽快帮助患者。

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.