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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DK088518-03
Application #
8332273
Study Section
Special Emphasis Panel (ZDK1-GRB-W (J1))
Program Officer
Castle, Arthur
Project Start
2010-09-06
Project End
2013-09-05
Budget Start
2012-09-06
Budget End
2013-09-05
Support Year
3
Fiscal Year
2012
Total Cost
$47,232
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Kim, Jaeyun; Li, Weiwei Aileen; Sands, Warren et al. (2014) Effect of pore structure of macroporous poly(lactide-co-glycolide) scaffolds on the in vivo enrichment of dendritic cells. ACS Appl Mater Interfaces 6:8505-12
Kim, Jaeyun; Bencherif, Sidi A; Li, Weiwei Aileen et al. (2014) Cell-friendly inverse opal-like hydrogels for a spatially separated co-culture system. Macromol Rapid Commun 35:1578-86