Human Thymic epithelial cells (TyEpiC) are vital regulators of thymocyte development and T lymphocyte (T-cell) tolerance. The thymus contains two types of TyEpiC; cortical and medullary thymic epithelial cells, which regulate the positive selection of thymocytes and the negative selection of autoreactive T-cells. The inability of TyEpiC to remove autoreactive T-cells in the thymus can affect self-tolerance and contribute to the development of autoimmune diseases such as myasthenia gravis, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. Human Thymic Epithelial Cells are an excellent in vitro model to study the mechanisms that modulate TyEpiC functionality; but also to develop targeted treatments for autoimmune disorders.