Grant: Operating Grant

Chronic inflammation is a characteristic feature of several chronic diseases including arthritis. It arises when activation signals in cells of our immune system predominate over inhibitory ones. Inhibitory signals are driven by proteins on the surface of immune cells known as inhibitory receptors. These proteins dampen the inflammatory response by switching off activation pathways rendering them attractive therapeutic targets. Even though inhibitory receptors play an important role in the immune response, we know very little about the role these proteins play in chronic inflammatory diseases. Our findings indicate that the inhibitory receptor MICL plays a key role in chronic inflammatory diseases such as rheumatoid arthritis. We reported a potential genetic association between MICL and rheumatoid arthritis. Also, our analysis of MICL in patient samples strongly suggest a role for this protein in this chronic disease. Even though we know that MICL dampens cell activation so that our immune cells are not activated for no reason, we still do not know how this protein works and how it can cause disease when it malfunctions or the cells gets rid of it for the wrong reason. The goal of this proposal is to determine how MICL controls cell activation, in part, by identifying the signals it sends into the cells. These findings will help us determine the role of MICL in rheumatoid arthritis through the analysis of patient samples as well as studies in various cellular systems. The novelty of our findings will provide new insights into the disease process of rheumatoid arthritis and potentially other chronic inflammatory diseases driven by cells that express MICL.