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Publication : Twist2 promotes CD8<sup>+</sup> T-cell differentiation by repressing ThPOK expression.

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.
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