Regulation of inflammation by homeostatic cholesterol transport pathways.

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Our body's response to infection and injury is centrally regulated by inflammation, a protective physiological response which is characterized by redness, swelling, heat, and pain, yet helps eliminate infection, clear out dead cells and tissues, and initiate tissue repair. However, perturbations in pathways that control inflammation can give rise to several chronic diseases including atherosclerosis, rheumatoid arthritis, and diabetes amongst others. Therefore, inflammation needs to be tightly regulated. As we age, our ability to regulate different physiological processes, including how we process dietary nutrients, declines, therefore exhibiting metabolic configurations previously unseen by the immune system. Although our understanding of the major drivers of inflammation has increased, however, detailed metabolic pathways that regulate inflammation remain unknown. The main aim of this proposal is to understand how cholesterol metabolism regulates inflammation. Increased cholesterol deposition is often a consequence of sedentary lifestyle and our studies suggest that cholesterol also contributes to the progression of the inflammatory process through mechanisms hitherto unidentified. We will study in-depth how cholesterol drives inflammation and how we may be able to develop treatments to prevent or slow this event. Cholesterol has a significant impact on health and treatment costs because of the associated risk of cardiovascular disease. Thus, understanding the roles of cholesterol in inflammation will help design better strategies to treat disease effectively.