Mesenchymal stem cells (MSCs) are stem cells that can be isolated from many tissues in the body, including fat. MSCs are being used in clinical trials for a number of inflammatory and immune-mediated diseases in both animals and people. In the primary investigator’s lab, they study how MSCs decrease inflammation and counteract the activation of immune cells that can harm the body’s own tissues (immune-mediated damage). They use naturally occurring inflammatory diseases in companion animals to determine the safety and effectiveness of MSC therapy. In a current clinical trial to treat severe inflammation of the mouth in cats, this researcher found that MSC therapy is safe and often curative (~75% of cats). In this clinical trial, and in complementary tests in the laboratory, they discovered that MSCs act on a specific subset of immune cells (activated T cells) and decrease their proliferation, activation and even shift them from a T cell that initiates inflammation to a T cell that dampens inflammation. In this study, they will determine how MSCs both directly (by actually binding to T cells) and indirectly (by secreting potent mediators) decrease T cell proliferation and activation. This researcher will also investigate one novel pathway by which MSCs may effectively “reprogram” the lymphocytes and result in long-term cure in cats with severe inflammation in their mouths. These findings will help them determine what other inflammatory or immune-mediated diseases in cats may benefit from MSC therapy.