Figure 1.

The hypothetical model for the development and functions of mTECs and molecules to promote the mTEC development. Bipotent common progenitors give rise to the mTEC progenitors expressing claudin-3 and -4. Lymphoid tissue inducer (LTi), Vγ5⁺ DETC progenitor (Vγ5⁺) or positively selected α β T cells produce RANKL; CD40L is supplied only by α β T cells. The interaction between RANKL and RANK promotes the differentiation and/or proliferation of the mTECs. The similar contribution of the interaction of CD40L and CD40 begins at the neonatal stage. RANK and CD40 signaling results in the translocation of the NF-κB family member RelB through the activation of signal transducers TRAF6 and NIK. The mature mTECs express a wide variety of tissue-specific antigens (TSAs) and AIRE. The TSAs are in part transferred to conventional DCs; as a result, both the mTECs and DCs would display the TSA-peptides to the developing T cells. The T cells expressing TCR bound to the complex of the TSA-peptide and MHC molecules with high avidity undergo apoptosis. Mature mTECs might further differentiate into involucrin-expressing mTECs in the LtβR and AIRE-dependent process. The LtβR signaling might regulate the up-regulation of RANK in the TECs and/or enhance the proliferation of the RANK-expressing TECs. Ligands and receptors involved in each process are surrounded by red line rectangles, signal transducers are by green line rectangles, transcription factors are by blue line rectangles.