A properly functioning immune system must be able to recognize foreign invaders among the multitude of cells in the body. This ability is essential to both fight infection and prevent autoimmune diseases. We study how a specific type of immune cells, known as T cells, are educated to make this distinction during development.
The thymus generates and selects a highly variable yet specific T cell repertoire which discriminates between self and non-self antigens. Within the thymus, medullary thymic epithelial cells express a diverse set of antigens, representing essentially all tissues of the body. This phenomenon, termed promiscuous gene expression, imposes central T cell self-tolerance by enabling peripheral antigens to be continuously accessible to developing T cells.
Ultimately, understanding the physiological mechanisms that lead to self-tolerance will be crucial in understanding autoimmunity and autoimmune diseases. Despite extensive work on the molecular basis of promiscuous gene expression, many questions concerning both single cell and tissue level organisation of antigen expression are unanswered. For instance, is promiscuous gene expression organised in a spatially or temporally restricted manner or a combination of both? How do thymic epithelial cells maintain their integrity despite expressing peripheral proteins that may interfere with epithelial-specific pathways and roles?
My research group seeks to answer these questions by combining genomics and mathematical modeling. We investigate the spatial and temporal organisation of promiscuous gene expression in the thymus and how antigen distribution in the thymus affects epithelial-T cell interaction and migration. Analogously, on single cell level, we conduct research on the spatio-temporal organisation of promiscuous gene expression to understand cellular integrity mechanisms in thymic epithelial cells.
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