Programming antigen specific dendritic cells in situ for type 1 diabetes immunoth

Harvard University, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): In the United States an estimated 23.6 million people have diabetes, of those 5-10% have type 1 diabetes and within a year approximately 15,000 individuals under the age of 20 will develop type 1 diabetes. Despite recent advances in pharmaceutical development and in organ transplantation, no treatment options exist to generate a durable cure for type 1 diabetes without causing substantial side effects. Autoimmunity remains a significant challenge in developing a cure for type 1 diabetes. The immunity in type 1 diabetes is the result of chronic activation of islet-specific T cells, leading to the eventual destruction of the islets and the development of diabetes. Dendritic cells (DC) are key players in the immune system that direct T cell responses and, in the setting of autoimmunity, have been shown to be important for developing both immunogenic and tolerogenic responses. We theorize that by both targeting and programming DC in the presence of antigen through the release of recruitment factors and by locally controlling the DCs microenvironment, potent tolerogenic responses can be developed. In other words, in this proposal we hypothesize that a material system that controls the spatiotemporal presentation of a recruiting factor, programming factor, and antigen can direct dendritic cells to a tolerogenic fate and lead to islet specific tolerance, the prevention of islet loss, and the attenuation of islet destruction in a murine model of type 1 diabetes. PUBLIC HEALTH RELEVANCE: Type 1 diabetes affects 1 to 2 million people in the United States and the number of people with the disease is growing at an increasing rate. Unfortunately, over time the disease damages the blood vessels leading to significant morbidity and a cure without substantial side effects does not exist. The goal of this research is to reprogram the immune system to prevent the onset or to cure type 1 diabetes.