Grant: Operating Grant

The immune system possesses the unique capacity to protect us from a broad range harmful threats including microbes, parasites and cancer. Dysfunctional immunity makes us susceptible to these threats and misdirected immune responses can cause disease and suffering through detrimental immunopathological reactions, seen in diseases such as inflammatory and autoimmune conditions. All immune responses are not created equal, and for the maintenance of health, the immune system must strike a balance between effective responses to serious threats and pathological responses. In order to achieve this balance each immune response must be tailored to the type of threat or invasion the body faces. At the heart of the immune response are dendritic cells, which possess powerful capabilities to determine the type of immune response that will develop. Dendritic cells integrate information from the environment, such as pathogen type and inflammatory mediators, and become differentially activated depending on the type of stimuli they receive. Through this differential activation, dendritic cells are able to transmit pathogen/threat-specific information to other components of the immune system. Work described in this proposal will study novel mechanisms which regulate dendritic cell function and therefore regulate the development of specific types of immune responses. Specifically, we will study a transcriptional repressor which keeps dendritic cells in a resting state; we will study how cellular metabolism affects dendritic cell function; and we will examine the ability of Notch ligands, previously thought to instruct T cell responses, to regulate dendritic cell activation. This work will provide new insights into the creation and control of specific inflammatory microenvironments in both health and disease.