Grant: Project Grant

The current proposal is founded on the discovery of a new approach for the treatment of autoimmune disease (occurring when the white blood cells of our immune system mistakenly recognize and attack natural components of our own tissues). Traditionally, vaccines have been used to expand white blood cells affording protection against viruses, bacteria or cancer, or to delete white blood cells causing autoimmune diseases like type 1 diabetes (T1D). We have developed a new type of 'vaccine' based on nanotechnology (using particles thousands of times smaller than the size of normal white blood cell) that can stop anti-self immune responses by selectively expanding what we call 'autoregulatory' white blood cells. These 'autoregulatory' white blood cells put the brakes on the disease-causing autoimmune attack, by inhibiting the activation of all the disease-causing white blood cells, resulting in their complete suppression. As a result, these nanomedicines can blunt highly complex autoimmune responses in mice, including T1D, multiple sclerosis, primary biliary cirrhosis and arthritis, without causing generalized suppression of the immune system. Importantly, we have established that human disease-relevant nanomedicines can effectively trigger the expansion of human autoregulatory white blood cells in 'humanized' mice (mice carrying white blood cells from patients), indicating that this approach is applicable to humans. Here, we will dissect the cellular origin of the disease-suppressor cell type triggered by our nanomedicines, as well as the mechanisms and the downstream cellular targets through which it suppresses disease. We anticipate that these studies will open new lines of inquiry in immunity and autoimmunity and will expose novel cellular and molecular targets for therapeutic intervention in autoimmune disease.