Regulatory T cells (Tregs) are important safety controls on the immune system. They actively surveil and suppress immune responses against innocuous or self-antigens. This is a critical mediator of tolerance. In this project we seek to induce them by modulating the behavior a critical antigen presenting cell that dictates T cell development, dendritic cells (DCs). DCs uptake foreign substances and present them to naive T cells, but the phenotype of DC is critical for determining if a T cell becomes a standard activated T cell or suppressive Treg. In this project, we seek to determine what types of combinations of chemical signals are best for making a DC a more likely to generate Treg (also known as a tolDC). We have found that combinations of immune activating compounds in combination with immune inhibitory (what we call Push/Pull Immunomodulation or PPI) work best at inducing tolDCs. We are currently in the process of screening new formulations using a large library of compounds, developing novel delivery systems, such as sustained released microparticles or lymph node targeted liposomes, to deliver these drugs and testing their efficacy on autoimmune and transplantation models.
