Blunting complex immune responses like those leading to inflammatory bowel disease (IBD) without compromising the ability of our immune system to protect us against infections and cancer is a long-sought after, but daunting goal. The current proposal is founded on the discovery of a new paradigm in the treatment of autoimmune diseases (caused by the white blood cells of the immune system). Traditionally, vaccines have been used to expand white blood cells capable of affording protection against viruses, bacteria or cancer, or to delete white blood cells capable of causing autoimmune diseases. We have developed a vaccine that can cure at least two different autoimmune diseases (type 1 diabetes and multiple sclerosis) by selectively expanding what we call disease-specific autoregulatory white blood cells. These autoregulatory white blood cells then put the brakes on the disease-causing autoimmune attack by suppressing and killing another type of white blood cell of the immune system that is responsible for orchestrating immune responses, including disease-causing ones (the so-called antigen-presenting cells). Since the autoregulatory white blood cells expanded by the nanovaccine selectively target the antigen-presenting cells orchestrating a specific disease, rather than all antigen-presenting cells of the body, they cannot cause generalized suppression of the immune system. Human IBD is the result of a dysregulated immune response to gut bacteria. We have discovered that regulatory white blood cells targeting a protein expressed by gut bacteria can reset this balance and protect mice from experimental colitis. Here I will test the hypothesis that expansion of gut bacteria-specific autoregulatory white blood cells in vivo by treatment of mice affected with IBD with IBD-specific nanovaccines will blunt the progression of disease. If this hypothesis is true, this work will pave the way for development of therapeutic nanovaccines for the treatment of human IBD.