Grant: Project Grant

Our immune system works under two major rules: i) recognize and destroy pathogens ii) do not harm body's own cells. Failure of the first rule causes immunodeficiency whereas breach of the second rule leads to autoimmune diseases. White blood cells termed "T cells" play important roles in enforcing these rules. To perform this duty, T cells are guided by a group of cell surface sensors including "ICOS (inducible costimulator)". Highlighting the importance of ICOS in promoting immunity, humans lacking ICOS suffer from severe immunodeficiency repeatedly coming down to infections. However, some patients are affected by both immunodeficiency and autoimmune diseases such as rheumatoid arthritis. It has been puzzling how the lack of ICOS increases the chance of autoimmune attack in patients whose ability to fight pathogens is weakened. Using genetically modified mouse models, Dr. Suh's research team began to understand why: on one hand, ICOS supports "helper T cells" that facilitate immune responses against pathogens; on the other hand, it promotes a particular subset of "regulatory T cells" whose role is to stop autoimmune T cells from erroneously attacking body's own cells. Building up on these observations, Dr. Suh's team will elucidate what biochemical events ICOS evokes inside T cells and how those change T cells' behavior ultimately leading to immune disorders. This study will not only advance basic T cell biology but also help devise new ways to treat immunodeficiency and autoimmune diseases.