1. Twist2 promotes CD8 + T-cell differentiation by repressing ThPOK expression.
- Author
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Hwang S, Lee C, Park K, Oh S, Jeon S, Kang B, Kim Y, Oh J, Jeon SH, Satake M, Taniuchi I, Lee H, and Seong RH
- Subjects
- Animals, CD4-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes cytology, Cell Differentiation genetics, Gene Expression Regulation genetics, HEK293 Cells, HeLa Cells, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell metabolism, Repressor Proteins metabolism, Signal Transduction genetics, Signal Transduction immunology, Thymus Gland cytology, Thymus Gland immunology, Transcription Factors biosynthesis, Twist-Related Protein 1 metabolism, CD4-Positive T-Lymphocytes physiology, CD8-Positive T-Lymphocytes physiology, Cell Differentiation immunology, Gene Expression Regulation immunology, Repressor Proteins genetics, Transcription Factors genetics, Twist-Related Protein 1 genetics
- Abstract
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 B2 m-/- 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.- Published
- 2020
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