Grant: Operating Grant

The Italian scientist Bizzozero described platelets about 150 years - a tiny, plate-shaped (thus the name) component of blood on the ready to repair damage to blood vessels by triggering the formation of a blood clot. A normal platelet count in humans is approximately 150-400 x 10E9 per liter, making the platelets the second most abundant cellular lineage in the blood circulation after the red blood cells. Their large number and their capability to quickly release a vast arsenal of mediators strategically position the platelets to safeguard the blood and to interact with other cells, such as immune cells. In fact, while it was quickly understood by Bizzozero that platelets' main role is to prevent bleedings, it is only recently that platelets were described as active players in rheumatic diseases, including systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disease that affects multiple anatomical locations, including kidneys, blood vessels, skin, joints, lungs, liver, heart and the nervous system. It can be fatal, with cardiovascular diseases being the leading cause of death. The worldwide incidence of SLE is conservatively estimated at 12-104 cases per 100,000, mostly women. While there exists no cure for SLE, it is currently treated with immunosupression mainly with cyclophosphamide, corticosteroids and other immunosupressants. In this application, we aim to delineate novel mechanisms by which platelets can promote SLE. We are interested by a very small component released from the platelets, called the mitochondria. We recently found that these mitochondria can be highly pro-inflammatory. We thus hypothesize that the platelets actively participate in SLE via their release of mitochondria.