Research Description

Obesity is associated with chronic inflammation that contributes to the risk of developing type 2 diabetes, which is a state where the body’s cells become less sensitive to insulin, leading to elevated levels of glucose in the blood. Despite enhanced inflammation, the body’s immune defenses against many infectious diseases are often weakened in people with diabetes. As fat expands in obesity and insulin resistance develops, a type of immune cell known as T cells initially contribute to the elevated inflammation, but later become exhausted due to chronic activation. Exhausted T cells have reduced immune defense functions; however, how T cells in fat and in other parts of the body develop obesity-induced exhaustion is poorly understood. The central hypothesis of this study is that T cell exhaustion is caused by obesity and diabetes to restrain inflammation and insulin resistance, thus contributing to reduced immune defenses. This study will examine the roles of the inhibitory receptor B and T cell attenuator (BTLA) and dysfunction of mitochondria as causative agents in leading to obesity-associated T cell exhaustion. Studies in high-fat diet-fed mice will help address how BTLA and mitochondrial dysfunction contribute to T cell exhaustion in obesity. The proposed research will address the gaps in knowledge regarding T cell exhaustion in obesity and diabetes. Completing this study will identify novel treatment strategies that can improve immune responses and glucose regulation in people with diabetes.