Project 461209

Kidneys clean the blood and dispose in the urine of waste produced by all the cells of the body. About 20% of the blood pumped by the heart is filtered by kidneys at a given time. This translates into 180 liters a day on average that are purified by the kidneys. To do so, an abundant network of blood vessels are present in the kidneys. In previous work, our team showed that damage to the tiniest kidney blood vessels, called peritubular capillaries, is one of the most important cause of renal failure. This is especially true in patients who have received a kidney transplant. In these patients, damage to these small blood vessels at the time of transplantation can cause kidney grafts to stop working prematurely. We also found that some antibodies can damage these small blood vessels at the time of kidney transplantation. Antibodies help us fight infections but also help dispose of dead cells in organs that have been damaged. These ''disposal antibodies'', especially one that is called anti-LG3, can damage those very precious tiny vessels. In turn, damaged vessels will release small pieces of cells we call ''apoptotic exosome-like vesicles''. These pieces of cells activate the immune system to produce more harmful antibodies. This vicious cycle that can destroy permanently small blood vessels and cause renal failure. Our group was the first to characterize anti-LG3 antibodies and also the small pieces of cells that are released by injured blood vessels. We discovered that when kidneys enter this vicious cycle of injury, attraction of harmful antibodies and further injury, they also attract white blood cells that move into the kidneys to produce locally harmful antibodies. Here, we will study how to prevent these antibodies from damaging kidneys but also how to prevent kidneys and the immune system in general to produce antibodies harmful to small kidney vessels, with the hope of making kidney transplants work better and longer.