Crosstalk between thymocytes and thymic epithelial cells is critical for T cell development and the establishment of central tolerance.Medullary thymic epithelial cells(mTECs) play important roles in the late stage of T cell development,especially negative selection and Treg generation.The function of mTECs is highly dependent on their characteristic features such as ectopic expression of peripheral tissue restricted antigens(TRAs) and their master regulator-autoimmune regulator(Aire),expression of various chemokines and cytokines.In this review,we summarize the current understanding of cellular and molecular mechanisms of mTEC development and its functions in T cell development and the establishment of central tolerance.The open questions in this field are also discussed.Understanding the function and underlying mechanisms of mTECs will contribute to the better control of autoimmune diseases and the improvement of immune reconstitution during aging or after infection,chemotherapy or radiotherapy. Crosstalk between thymocytes and thymic epithelial cells is critical for T cell development and the establishment of central tolerance. Medullary thymic epithelial cells (mTECs) play important roles in the late stage of T cell development, especially negative selection and Treg generation. The function of mTECs is highly dependent on their characteristic features such as ectopic expression of peripheral tissue restricted antigens (TRAs) and their master regulator-autoimmune regulator (Aire), expression of various chemokines and cytokines. in this review, we summarize the current understanding of cellular and molecular mechanisms of mTEC development and its functions in T cell development and the establishment of central tolerance. the open questions in this field are also discussed. Unnderstanding the function and underlying mechanisms of mTECs will contribute to the better control of autoimmune diseases and the improvement of immune reconstitution during aging or after infection, chemotherapy or r adiotherapy.