Final Report Summary - MICROINNATE (An exploration into the role of microRNAs in innate immune signaling)
This project concerns the complex regulation of the innate immune system. Our immune systems protect us from infection and also repair damage to tissues that occurs either during infection, or in response to trauma. However, this process can become dysfunctional for largely unknown reasons, and give rise to a whole range of inflammatory diseases, which remain difficult to treat. Our work mainly concerned key immune regulators called miRNAs, which are important 'off switches' in immunity. We found that one of these, termed miR155, was important for controlling inflammation at different times of the day. Inflammation is known to vary with the time of day, being more severe at night for example, in diseases like asthma and arthritis. Our work on miR155 might help explain why these exacerbations occur and could lead to better treatments. Starting with another miRNA termed miR210, we made another key finding, this time in the area of metabolism - the process whereby cells take up nutrients and use them for various functions, including supplying energy. What we found was remarkable - that instead of being used for energy production, a key structure in our cells termed mitochondria, become less able to make ATP for energy, but instead start to make damaging by-products called reactive oxygen species. This involves a metabolite called succinate, and we were the first to implicate this in immunity. This process can go out of control and could be critical for the development of conditions such as septic shock and rheumatoid arthritis. Our work has contributed to the emergence of the burgeoning field of immunometabolism. Our findings could be far-reaching, having possible implications for the development of new anti-inflammatory agents or agents to use in transplantation or cancer.