Twist2 promotes CD8+ T-cell differentiation by repressing ThPOK expression
| Autor: | Changjin Lee, Ho Lee, Sunsook Hwang, Sung Ho Jeon, Sangwook Oh, Rho Hyun Seong, Masanobu Satake, Ichiro Taniuchi, Kyung Soo Park, Jaehak Oh, Byeonggeun Kang, Yehyun Kim, Shin Jeon |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Regulator Locus (genetics) Cell Biology Biology Major histocompatibility complex Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system 030220 oncology & carcinogenesis biology.protein Cytotoxic T cell Receptor Molecular Biology Transcription factor CD8 |
| Zdroj: | Cell Death & Differentiation. 27:3053-3064 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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