The thymus represents a vital organ of the immune system, providing the primary site for T-cell development. The production of T-cells by the thymus has a direct impact on the capacity of the immune system to fight infectious agents and provide surveillance against cancer forming cells. Within the thymus, stromal cells provide unique signals to support the development of T-cells that are subsequently exported into the peripheral circulation. As peripheral T cells are continuously lost through attrition, continued production of T-cells by the thymus is critical for the maintenance of a diverse T-cell pool required for effective, lifelong immune protection against diverse infectious challenges. The central role of thymic stromal cells in the regulation of T-cell development is highlighted by the breakdown of T-cell mediated immunity and the manifestation of autoimmunity that can occur in both human patients and animal models possessing defects in thymic stromal cell development and function.
The primary research focus of the lab is to investigate mechanisms regulating the development and function of thymic stromal cells and determine how this impacts T-cell development, immune protection and autoimmune disease. The significance of understanding, and potentially manipulating thymic stromal cell development and function, may have important implications for attempts to improve T-cell development in settings of diminished T-cell immunity and associated susceptibility to infection such as occurs following irradiation therapy and subsequent bone marrow transplantation.
Thymic mesenchymal stroma
The size of thymic tissues directly correlates with the capacity of the thymus to produce new T-cells. Our previous research revealed that thymic mesenchymal stroma plays a critical role in driving the growth of functional thymic microenvironments, particularly during fetal stages. Our current research is aimed at further investigating how thymic mesenchyme contributes to thymic function and T-cell development in established thymus tissues, and how alterations in thymic mesenchyme may contribute to the loss of thymic function that occurs with increasing age.
Thymic epithelial stroma
Thymic epithelial cells critically regulate T-cell development via supporting the development, proliferation and selection of diverse, functional T-cells. Critically, thymic epithelium contributes to the prevention of autoimmune disease via deletion of autoreactive T-cells and supporting the development of suppressive regulatory T-cells. Ongoing research within the lab is aimed at defining the developmental pathways of thymic epithelial cells, including investigation of thymic epithelial progenitor and stem cell populations and the cellular and molecular interactions that control the differentiation and maintenance of such cells.
T cell development
T-cell development is intrinsically linked to thymic stromal cell function. The regulated interaction of immature, developing T-cells with functionally distinct thymic stromal subsets is critical for effective T-cell production. Our research in this area includes investigation of the mechanisms that control the migration of T-cell progenitors and their progeny into, within and ultimately out of thymic tissues and the processes that contribute to the intrathymic selection of self-tolerant, functional T-cell subsets.