cGAS-STING driven activation of type-I interferon in Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome affects young boys below 10 and it is a severe immune deficiency complicated by autoimmunity. The current curative options include bone marrow transplantation of matched donors or gene corrected stem cells. One the long lasting complication of the disease is represented by autoimmune manifestations that are often treated by non-specific immunosuppressive medicaments that collide with immune deficiency. Therefore it exists an urgent need to identify the origin of autoimmunity to tailor personalized intervention. Our preliminary data show that excessive inflammation and WAS autoimmunity may arise from erroneous recognition of endogenous DNA contained within our body's cells as an enemy. The central system that recognize and initiate immune responses against endogenous DNA is called cGAS-STING. In this project we  aim to understand the reasons for malfunctioning of cGAS-STING in WAS mutant cells and to explore ways to correct it. In addition we will analyze novel parameters to score patients based on the presence of inflammatory profiles in their blood cells in order to personalize the curative options.