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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 [3]. Studies have shown that changes in the expression of tumor necrosis factor receptor family members and transcription factors Foxn1 and autoimmune regulator (Aire) can alter the thymic microenvironment and self-tolerance. Human TyEpiC are an excellent in vitro model to study the mechanisms that modulate TyEpiC functionality and to develop targeted treatments for autoimmune disorders.