Defining the role of CAR in lung homeostasis and response to inflammation

英国有超过500万人患有哮喘或各种过敏性炎症性肺部疾病，这些疾病会影响他们正常呼吸的能力。这些疾病可能对生活质量产生重大影响，在最严重的情况下可能致命。一些患有哮喘和炎症性肺病的人可以使用吸入类固醇治疗，这有助于扩张气道，缓解呼吸问题。然而，这些疾病的长期治疗方法或对类固醇无效的治疗方法仍然不可用。此外，我们仍然不了解在过敏触发反应后导致肺部炎症的许多因素。更多地了解这些因素对于开发有助于治疗这些炎症性肺部疾病的新药非常重要。我们已经确定了一种叫做CAR的蛋白质，它存在于肺气道的细胞（上皮细胞）中。在健康的肺中，CAR在帮助这些细胞形成保护肺组织的屏障方面很重要。然而，我们已经证明，当肺部暴露于引发炎症的因素时，CAR会改变它的功能，比如室内尘螨，超过50%的患者会引发哮喘。我们已经证明，在接触尘螨后，CAR实际上促进了免疫细胞向肺部的募集，如果我们去除或阻断这些细胞中的CAR，炎症就会减少。减少炎症的数量非常重要，因为它可以阻止严重哮喘患者出现临床特征。因此，CAR作为控制肺部炎症的潜在关键因素，是一个非常好的候选因子，值得进一步探索。我们目前的项目将研究CAR控制暴露于室内尘螨后招募到肺部的免疫细胞的方式。我们还将测试阻断CAR功能的药物是否可以阻止免疫细胞向肺的募集。我们的研究将为治疗哮喘和其他炎症性肺部疾病提供一个新的潜在治疗靶点，并有可能为未来对抗这些疾病的药物开发提供新的途径。

Over 5 million people in the UK suffer from asthma or forms of allergic inflammatory lung diseases that affect their ability to breathe properly. These disorders can have a significant impact on quality of life and in the most severe cases can be fatal. Some people with asthma and inflammatory lung diseases can be treated using inhaled steroids, which can help to expand the airways and alleviate breathing problems. However, long-term cures for these disorders or treatments for those who do not respond to steroids are still not available. Moreover, we still do not understand many of the factors that contribute to inflammation in the lungs following responses to allergic triggers. Understanding more about these factors is very important in enabling new drugs to be developed that can help treat these inflammatory lung disorders. We have identified a protein called CAR that is present in the cells that line the lung airways (called epithelial cells). In healthy lungs, CAR is important in helping these cells to form a barrier to protect the lung tissue. However, we have shown that CAR changes it's function when lungs are exposed to factors that drive inflammation, such as house dust mites which can trigger asthma in over 50% of patients. We have shown that CAR actually promotes the recruitment of immune cells to lungs after exposure to house dust mite and if we remove or block CAR in these cells, the inflammation is reduced. Reducing the amount of inflammation is very important as it stops the onset of the clinical features seen in severe asthma patients. CAR is therefore a very good candidate factor for further exploration as a potential key factor controlling inflammation in the lung. Our current project will investigate the way that CAR controls the immune cells that are recruited to the lung after exposure to house dust mites. We will also test whether agents that block the function of CAR can prevent the recruitment of immune cells to the lung. Our studies will characterise a new potential therapeutic target for the treatment of asthma and other inflammatory lung diseases and will potentially provide new avenues for the development of drugs to combat these disorders in future.