Dendritic Cell-Targeted Immunomodulation for Tolerance

This presentation will highlight results from our biomaterials and molecular based approaches to direct the immune system toward tolerance. Microparticle-based systems have been designed as injectable vaccines to retrain the immune system to correct aberrant activation toward self-antigens. Hydrogels and microparticles with encapsulated immunomodulatory factors and antigen provide targeted, controlled delivery in vivo to both intracellular and cell surface targets of immune cells, dendritic cells in particular, in order to promote tolerance. Using a microparticle formulation consisting of a combination of suppressive factors we have demonstrated prevention and reversal of type 1 diabetes in non-obese diabetic mice, as well as treatment of multiple sclerosis in an EAE mouse model. Investigations into the immunological mechanisms implicate a role for regulatory T cells and B cells. In addition, we are developing molecular engineering approaches to direct tissue-localized metabolism to guide immune cell function toward tolerogenic phenotypes.