Keeping the immune system in line
Working on autoimmune diseases, Dr Lu Liwei (Croucher Senior Research Fellowship 2012) is developing more specialised treatments for lupus, rheumatoid arthritis, and Sjögren’s syndrome. His work on modulating the function of immune system also spreads into developing treatments for influenza infections.
Following a general trend in medicine towards more specialised, targeted treatments, Lu’s research seeks to focus in on the direct causes of autoimmune disorders. Because of the chronic nature of diseases like lupus or rheumatoid arthritis and the lack of a true cure, general treatment with immunosuppressive drugs is often used just to manage the symptoms of the disease. However, using mouse models, Lu is looking into treating these autoimmune diseases through gene silencing and targeted attacks on the overzealous immune cells that cause the disease.
Although the exact cause of rheumatoid arthritis is still unknown, Lu’s research has revealed the exacerbatory effect that the hormone leptin has on arthritis. Produced by adipocytes (fat cells), leptin is usually known as the “satiety hormone”, signalling to the brain that one is full. However, leptin also significantly increases the generation of proinflammatory cytokines from Th17 cells (a class of helper T cells in immune system). Lu’s research shows that mice injected with leptin show an increase in the activity of these Th17 cells and a decrease in function and activation of Treg cells (the cells that regulate the immune system defences, preventing autoimmune attacks). Lu hopes that his research will help in the development of a treatment course to help subdue adipocytes, reducing leptin production in joint tissue and the effect they have on the progression and severity of the disease.
Lupus and Sjögren’s syndrome are two other autoimmune diseases that Lu’s research team is working on. While lupus is more well known, there is still no real cure method outside of just managing symptoms. Sjögren’s syndrome is another autoimmune disease often associated with rheumatoid arthritis and lupus that causes the body’s immune system to attack the cells that produce saliva and tears. Lu’s recent research on Sjögren’s has led to the development of a new mouse model useful for studying this disease and the identification of Th17 cells as a key player in disease development. He hopes to use the knowledge gained to put together a more specific treatment course for the syndrome, as right now only general therapies for other related diseases are used. Currently, Lu is also collaborating on a National Key Research Program sponsored by the Ministry of Science and Technology of China focusing on the function of B cells in lupus development.
B cells and influenza
B cells represent one of the first lines of defence the body has against invading pathogens. Generally speaking we have two types, B-1 and B-2 cells. B-2 cells freely circulate through our blood, acting like patrolling security guards. B-1 cells, on the other hand, reside in pleural cavities like the folds in our lungs and, while poorly studied overall, are known to be important for localised inflammation and immune response. With regards to influenza, Lu is researching the ways that B-1 cells in the lungs differentiate after infection with the hope that the introduction of cytokines (via intranasal administration) that can enhance B-1 cell function and local immune response will aid in the body’s fight against the invading influenza.
Dr Liwei Lu completed his undergraduate studies at the Jiangsu University medical school before moving on for his PhD at McGill. He did his postdoctoral fellowship at the University of Toronto after which he joined the Department of Pathology at the University of Hong Kong, where he is a full professor of immunology.
To view Dr Lu’s personal Croucher profile, please click here.