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 to deliver these drugs and testing their efficacy on autoimmune and transplantation models.
