Grant: Project Grant

Lymphedema is a condition of uncontrolled fluid accumulation and tissue swelling that affects ~140 million people worldwide. Lymphedema can cause discomfort, immobility and organ dysfunction. Edematous tissue in lymphedema presents a high risk of infection. The major cause of lymphedema in the world is lymphatic filariasis. In Canada, the major cause of lymphedema is the damage to the lymphatic vessels and LNs associated with cancer and cancer therapies, which impacts almost all of the cancer types that involve cancer spread via the lymphatic vessels. Infection and obesity are the major risk factors of lymphedema in cancer survivors: 38-89% of breast cancer patients will eventually develop lymphedema. Currently, there is no cure for lymphedema, mainly due to the lack of mechanistic understanding of its development. Some lymphedema patients exhibit significant body disfigurement and need life long intervention with compression garments, which cause a huge psycho-social and economic impact on these patients. The lack of knowledge regarding the regulation of lymph flow has been the barrier for the disease prevention or treatment. Lymphatic vessels maintain fluid balance and transport tissue waste, pathogens and cells to lymph nodes for protection by the immune system. In the lymph node, lymph flow direction determines the time, the location and the cell types that antigens will encounter after immune stimulation. Lymph nodes are typically surrounded by fat tissue and I have found that this perinodal fat may partially compensate for the immune protection function when lymph flow via lymphatic vessels is compromised. In this study, I will determine how fat tissue around the LN participates in fluid balance and combating bacterial infection when lymphatic vessel function is compromised. Our work aims to target perinodal adipose tissue in order to develop potential therapeutic methods to reduce edema and improve host immune protection.