Fig. 2.

Development of thymic epithelial cells is induced by various subsets of thymocytes. cTECs and mTECs arise from common progenitor TECs (pTECs) in endodermal epithelium from the third pharyngeal pouch. pTECs differentiate into ‘transitional’ pTECs that express cTEC-associated genes such as β5t and IL-7. This process is critically regulated by the transcription factor FoxN1 but independent of lymphocytes. Thymocyte development beyond DN1 induces maturation of cTECs expressing high levels of β5t. The development of mTECs is triggered in embryonic thymus by LTi cells and γδT cells that express RANKL. In postnatal thymus, SP thymocytes and NKT cells express RANKL to promote the differentiation and proliferation of Aire-expressing mTECs. RANKL-stimulated mTECs produce OPG to self-tune their development. CD40L expressed in CD4SP thymocytes cooperates with RANKL to promote mTEC development. CD4SP thymocytes also express LTs, which induce terminal differentiation of mTECs