Comparing the mechanism of skin and synovial tissue inflammation in psoriatic arthritis

银屑病关节炎是一种以皮肤和关节炎症为特征的疾病。它发生在30%的皮肤病牛皮癣患者中，是炎症性关节炎的第二大常见原因。在银屑病关节炎中，皮肤和关节中的免疫细胞过度活跃，导致炎症和损伤。目前尚不清楚是什么引发或驱动这种炎症，或者皮肤和关节炎症的潜在机制是否相同。该项目的目的是比较引起皮肤炎症的免疫细胞与引起关节炎症的免疫细胞。免疫细胞表达一种特异性受体，使它们能够识别并结合被识别为“非自身”的蛋白质。当受体与这种蛋白质结合时，免疫细胞被激活并产生多种引起炎症的产物（“细胞因子”）。免疫细胞也开始分裂，产生多个表达相同受体的细胞。我们预测，在银屑病关节炎中，引起皮肤炎症的免疫细胞表达与关节中相同的受体并产生相同的细胞因子。为了调查这一点，我们将要求银屑病关节炎患者捐献血液样本和发炎的皮肤和组织衬里发炎关节的样本。我们将从这些样本中分离出感兴趣的免疫细胞，并单独分析每个细胞，以鉴定其表达的受体和产生的细胞因子。我们希望找到表达相同受体的免疫细胞群存在于炎症部位，即发炎的皮肤和发炎的关节，而不是血液。我们还希望发现这些免疫细胞群在皮肤和关节中表达相同的细胞因子，这项研究将提高我们对银屑病关节炎中引起皮肤和关节炎症的细胞及其产生的细胞因子的认识。这可能导致识别新的治疗靶标（例如新的抗细胞因子策略）。此外，了解哪些受体在炎症组织中过度激活可能会导致进一步的研究，以确定激活这些受体的蛋白质。这反过来可能导致称为肽免疫疗法的治疗方法的发展，以防止这些特定受体的激活并减少或预防炎症。这将是一个令人兴奋的新的治疗选择银屑病关节炎。

Psoriatic arthritis is a disease characterised by inflammation in the skin and the joints. It develops in 30% of people with the skin condition psoriasis and is the second commonest cause of inflammatory arthritis. In psoriatic arthritis the immune cells in the skin and the joints are over-active leading to inflammation and damage. Currently it is not known what initiates or drives this inflammation or if the mechanisms underlying inflammation in the skin and the joints are the same.The aim of this project is to compare the immune cells causing inflammation in the skin with those causing inflammation in the joints. Immune cells express a specific receptor that allows them to recognise and bind to proteins that are recognised as "non-self". When the receptor binds to such a protein the immune cell becomes activated and produces a variety of products ("cytokines") that cause inflammation. The immune cell also starts to divide to produce multiple cells all expressing the same receptor. We predict that in psoriatic arthritis the immune cells causing inflammation in the skin express the same receptors and make the same cytokines as those in the joints. To investigate this we shall ask patients with psoriatic arthritis to donate blood samples and samples of inflamed skin and tissue lining inflamed joints. We shall isolate the immune cells of interest from these samples and analyse each cell individually to identify the receptor it expresses and the cytokines that it makes. We expect to find groups of immune cells expressing the same receptors to be present at the sites of inflammation i.e. the inflamed skin and inflamed joints but not the blood. We also expect to find that these groups of immune cells will express the same cytokines in both the skin and the joints.This study will improve our knowledge of the cells causing inflammation in the skin and the joint in psoriatic arthritis and the cytokines they produce. This may lead to the identification of new targets (for example novel anti-cytokine strategies) for treatment. Furthermore, knowledge of which receptors are over-activated in inflamed tissue could lead to further studies to identify the protein(s) that activate these receptors. This in turn could lead to the development of treatments known as peptide immunotherapy to prevent the activation of these specific receptors and decrease or prevent the inflammation. This would represent an exciting new treatment option for psoriatic arthritis.