Grant: Operating Grant

The immune system plays a multi-faceted role in determining how the body reacts appropriately to pathogens (immunity), environmental triggers (allergens) and normal versus foreign tissues (such as a fetus in pregnancy versus transplant rejection). An intricate network of triggers including immune hormones called cytokines, regulate these outcomes. Loss of control of these cytokines or the biochemical pathways they activate can lead to diseases, such as autoimmunity, immune deficiencies and inadequate response to infection. Treating diseases with few side effects requires knowing the molecular processes involved in disease development. The cytokine IL-7 is a major immunotherapeutic undergoing clinical trials for cancer, immune restoration after transplantation or HIV and hepatitis C viral infection. We use gene-targeted mouse models to identify the steps that that are controlled by IL-7 that are necessary for normal lymphocyte development and immune responses to microbes. By interrupting specific signals in a biochemical pathway, we examined whether the disruption affected normal cells and found some important effects on immune response to pathogens. A better knowledge of cytokine signaling in vivo will further our understanding of lymphocyte regulation to help identify potential therapeutic strategies to cancer and to enhance immunity against infections.