Fig. 2. Transcriptional regulation in the development of CD4CD8αα DP IEL. Runx3, known as a key transcription factor for CD8 T cell lineage, which are normally repressed in conventional CD4 T cells, can be reactivated in peripheral CD4 T cells by gut environmental factors including TGF-β and RA and T-bet. Runx3 repressess ThPOK, a transcription factor for CD4 T cell lineage, through direct binding to ThPOK silencer elements, thereby promoting CD8αα and CD103 expression and CTL-associated gene program in the CD4 T cells.