Grant: Operating Grant

Inflammatory diseases are common and debilitating and involve all parts of the body. For example, inflammation of the joints is called arthritis and causes pain and loss of mobility. Inflamed or infected intestines occurs with colitis and is manifest by pain, diarrhea and weight loss. Asthma features inflamed lung airways. Blood vessels are inflamed in atherosclerosis and causes heart attacks, strokes, blindness and poor circulation. In fact, any organ may become inflamed for a short or long time and this affects the well-being of millions of people. There is an urgent need for effective treatments for these diseases. In our lab, we identified a protein known as CD248, that is made by cells (stromal and perivascular cells) that are normally resident in all tissues. These cells only make CD248 when inflammation is present, suggesting that CD248 might make the inflammation worse. We tested this by generating mice that lack CD248. These CD248 "knockout" mice are resistant to inflammation in a model of arthritis, i.e. the inflammation was much less severe. This is a very important finding: With this information, drugs may eventually be designed that decrease the effect of CD248, which in turn will decrease the arthritis and hopefully other inflammatory disorders. Our goal is to learn how CD248 decreases inflammation. To do this, we will use various biochemical methods to determine what proteins attach to different parts of CD248 and how the cells switch from being normal to inflamed. The studies will help us figure out how to better turn off the pro-inflammatory effects of CD248. We will also use mice models to determine which diseases are affected by changes in CD248 so that we can better devise therapies for the different diseases. We are confident that with the information gained, scientists will be able to design better ways to decrease the severity of the many diseases associated with inflammation, thereby improving health and quality of life.