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

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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.