ZFP36L1 – A candidate risk gene for autoimmune disease

Summary

Our immune system protects us from infections and guards against cancer. However, when it doesn't function properly, it can mistakenly attack our own body, leading to autoimmune diseases. Autoimmune conditions like rheumatoid arthritis and diabetes are complicated issues where different types of immune cells contribute to the disease and its severity. Their causes aren’t always clear, and can involve several factors such as infections, diet and gut bacteria. Some specific genetic variations have also been found that make it more likely for someone to develop an autoimmune disease.

We’ve found that genetic variations affecting a gene called ZFP36L1 are associated with several autoimmune diseases. In mice, we found that having the right amount of ZFP36L1 protein (the product of the gene) is crucial for balancing the strength of their immune response to infections. Too much ZFP36L1 protein leads to a weak immune response which cannot fight the infection properly, while too little results in an excessive immune response which damages tissues of the body. We believe these results in mice might help to explain why ZFP36L1 is associated with human autoimmune diseases. A potential scenario is that genetic variations that lead to lower amounts of ZFP36L1 protein being produced could result in immune cells that are out of control and so are more likely to start attacking our own tissues, causing the development of an autoimmune disorder.

We plan to examine how much ZFP36L1 is produced in specialized immune cells (called T cells) from healthy individuals who have these genetic variations, and how these T cells respond to immune stimulatory triggers.

We believe that understanding how ZFP36L1 levels influence T cell responses could help us develop new ways to diagnose or predict autoimmune diseases. Additionally, our research could provide valuable insights into how these diseases progress, which could guide future treatments.