Mucosal Immunology Group
The group focuses on two main areas of Research
Area 1: Mucosal Immunology
The intestinal mucosa represents the largest surface of the body and is continually exposed to foreign antigen derived from our diet and the estimated 10*14 microorganisms residing within the intestinal lumen. Maintenance of intestinal homeostasis is critically dependent upon the immune system’s ability to remain tolerant to these antigens while retaining the ability to mount appropriate immune responses to the many viral, parasitic and bacterial pathogens that utilize the intestine as a primary site of entry into the host. Importantly a breakdown in such mechanisms can result in intestinal pathology and is believed to contribute to the development and maintenance of inflammatory bowel diseases including Crohn’s disease and ulcerative colitis, as well as food hypersensitivities such as celiac disease. The project focuses on understanding the mechanisms regulating mucosal immune responses in health and disease with an aim to finding novel modalities for the treatment of human disease and vaccine therapies against mucosal pathogens. Our particular focus is on the role of dendritic cells and macrophage subsets in the regulation of mucosal T cell responses and T cell migratory behavior.
Area 2: T cell development
T cells are key cellular components of the adaptive immune system that play a critical role in our defense against pathogens and cancer but also contribute to pathology in the setting of chronic inflammation and autoimmunity. T cell development takes place in the thymus where bone marrow derived precursors undergo a well defined program of differentiation and positive and negative selection that ensures the generation of T cells with potentially useful T cell receptor (TCR) repertoires and the deletion of autoreactive T cells; a process that is essential to maintain immune homeostasis and prevent autoimmunity. The ordered development of T cells requires interactions between developing thymocytes with thymic epithelial cells (TECs) in the thymic cortex and medulla. In addition thymic stomal cells provide important queues for the development of TECs as well as thymocyte entry and exit. The project focuses on the ontogeny and function of thymic stromal cells in the regulation of TEC and thymocyte development.