Characterisation of a novel innate-like T cell in the eye as a target tissue in uveitis, spondyloarthropathy (SpA) and related diseases

葡萄膜炎是一种影响眼睛部分葡萄膜的疾病。全球约有22%的患者会出现疼痛的炎症、视力丧失和失明。葡萄膜炎主要发生在年轻或工作年龄的患者中，因此视力丧失和频繁去医院也使他们难以维持就业，并引起包括抑郁症在内的其他问题。40%患有脊椎关节病的患者也会发生葡萄膜炎。这是一种免疫系统疾病，影响关节、肌腱（连接肌腱和骨骼的结构）、眼睛、肠道和皮肤，并导致大量残疾。目前我们还不清楚葡萄膜炎发生的原因和方式。目前，葡萄膜炎的治疗方法很少。它们并不能治疗所有的病人，而且会产生严重的副作用，可能会导致失明。研究表明，存在于器官内部的一种免疫细胞，T细胞，可能是导致脊椎关节病引起的大部分疾病和残疾的原因，但我们不知道这是否适用于眼睛。如果我们知道眼睛中存在的导致炎症的免疫细胞类型，它将帮助我们设计出更好的治疗葡萄膜炎和脊椎关节病的方法。研究脊椎关节病不同组织中免疫细胞的异同，将有助于我们为脊椎关节病和葡萄膜炎患者设计最有效的治疗方案。对这些免疫细胞的研究已经成功地治疗了受脊椎关节病影响的器官，比如皮肤。我们的研究目标是使用新的方法来发现导致葡萄膜炎的免疫细胞和基因的类型，并根据我们的结果开发成功的治疗方法。我们对一种类型的T细胞特别感兴趣，这种细胞最近被研究小组成员发现存在于脊椎关节病中。肯尼迪风湿病研究所在研究引起身体炎症的疾病病因方面具有特殊的专长，包括脊椎关节病。我们的研究小组在一项名为“单细胞RNA测序”的尖端技术方面拥有专业知识，这将使我们能够使用相当少量的眼睛细胞来了解哪些基因和哪些细胞在炎症中变得活跃。这些信息可以像地图一样被查看，并告诉我们炎症的位置，哪些细胞引起了炎症，以及当眼睛发炎时哪些基因是活跃的。在脊椎关节病中，类似的细胞很可能会引起身体其他部位的炎症。我们可以分析这些基因和细胞的功能，以便了解葡萄膜炎和脊椎关节病是如何引起的，以及如何成功地控制它。我们希望这项研究能带来新的治疗方法。我们与许多专科外科中心达成协议，当他们进行称为小梁切除术的普通外科手术时，我们会提供一小部分眼睛样本。作为此类手术的一部分，该样本通常会被移除，虽然它通常会被丢弃，但我们现在已获得伦理批准，可以将其用于人眼单细胞RNA测序。这项研究将占用Sharma博士40%的时间，总共将持续33个月。Sharma博士在眼部研究和研究与葡萄膜炎和脊椎关节病有关的基因方面经验丰富。我们的研究团队由各领域的专家组成，以确保我们按时完成这项研究并获得最高质量的结果，最终帮助葡萄膜炎和脊椎关节病患者。

Uveitis is a condition affecting a part of the eye called the uvea. It causes painful inflammation, sight loss and blindness in about 22% of patients worldwide. Uveitis mainly occurs in patients who are young or of working age so sight loss and frequent visits to hospital also make it difficult to maintain employment and cause other problems including depression. Uveitis also occurs in 40% of patients suffering from a condition called spondyloarthropathy. This is a disease of the immune system affecting the joints, the entheses (the structures connecting tendons to bone), eyes, bowel and skin and causes a great deal of disability. Currently we do not understand why and how uveitis occurs. At present, there are very few treatments for uveitis. They do not treat all patients and can have serious side effects which can cause blindness in their own right.Research shows us that one type of immune cell, the T cell existing within the organ itself, could be responsible for much of the disease and disability caused by spondyloarthropathy but we do not know that this for the eye . If we knew the type of immune cell present in the eye which causes inflammation it would help us design much better treatments for uveitis as well as spondyloarthropathy. The similarities and differences between the immune cells in different tissues in spondyloarthropathy will help us design the most effective treatments for patients suffering from spondyloarthropathy as well as uveitis. Studying these immune cells has already resulted in very successful treatment for organs which are affected by spondyloarthropathy such as the skin. The goal of our research is to use new methods to discover the types of immune cells, and genes which are responsible for uveitis and to develop successful treatments based on our results. We are expecially interested in one type of T cell which has recently been found by members of the research team to be present in spondyloarthropathy.The Kennedy Institute of Rheumatology has special expertise in research into the cause of diseases which cause inflammation in the body including spondyloarthropathy. Our research group has expertise in a cutting-edge technique called 'single cell RNA sequencing' , This will allow us to use fairly small numbers of cells from the eye to understand which genes and which cells become active in inflammation. This information can be viewed rather like a map and will tell us where the inflammation is located , which cells are causing it and which genes are active when the eye becomes inflamed. It is likely that similar cells will cause inflammation elsewhere in the body in spondyloarthropathy. We can analyse the functions of these genes and cells in order to understand how uveitis and spondyloarthropathy is caused and how it might be successfully controlled. We expect this research will lead to new treatments.We have agreement from a number of specialist surgical centres to provide a small sample from the eye when they are performing a common surgical procedure called a trabeculectomy. This sample is routinely removed as a part of this type of surgery and while it is normally discarded, we now have ethical approval to use it for single cell RNA sequencing in the human eye. This research will take up 40% of Dr Sharma's time and will last for 33 months in total. Dr Sharma has experience in research in eyes and in studying genes involved in uveitis and spondyloarthropathy. Our research team consists of a wide variety of experts in their respective fields to make sure that we complete this research on time and get results of the highest quality and ultimately, to help patients with uveitis and spondyloarthropathy.