First Author | Hwang S | Year | 2020 |
Journal | Cell Death Differ | Volume | 27 |
Issue | 11 | Pages | 3053-3064 |
PubMed ID | 32424141 | Mgi Jnum | J:325253 |
Mgi Id | MGI:7284482 | Doi | 10.1038/s41418-020-0560-x |
Citation | Hwang S, et al. (2020) Twist2 promotes CD8(+) T-cell differentiation by repressing ThPOK expression. Cell Death Differ 27(11):3053-3064 |
abstractText | CD4/CD8 T-cell lineage differentiation is a key process in immune system development; however, a defined regulator(s) that converts the signal from T-cell receptor and co-receptor complexes into lineage differentiation remains unclear. Here, we show that Twist2 is a critical factor in CD4/CD8 thymocyte differentiation. Twist2 expression is differentially regulated by T-cell receptor signaling, leading to differentiation into the CD4 or CD8 lineage. Forced Twist2 expression perturbed CD4(+) thymocyte differentiation while enhancing CD8(+) thymocyte differentiation. Furthermore, Twist2 expression produced mature CD8(+) thymocytes in B2m(-/-) mice, while its deficiency significantly impaired CD8(+) cells in MHC class-II(-/)(-) and TCR transgenic mice, favoring CD8 T-cell differentiation. During CD8 lineage differentiation, Twist2 interacted with Runx3 to bind to the silencer region of the ThPOK locus, thereby blocking ThPOK expression. These findings indicate that Twist2 is a part of the transcription factor network controlling CD8 lineage differentiation. |