Twist2 promotes CD8+ T-cell differentiation by repressing ThPOK expression

• Published in: Cell death and differentiation Vol. 27; no. 11; pp. 3053 - 3064
• Main Authors: Hwang, Sunsook, Lee, Changjin, Park, Kyungsoo, Oh, Sangwook, Jeon, Shin, Kang, Byeonggeun, Kim, Yehyun, Oh, Jaehak, Jeon, Sung Ho, Satake, Masanobu, Taniuchi, Ichiro, Lee, Ho, Seong, Rho Hyun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2020; Nature Publishing Group
• Subjects: 13/1; 13/31; 14/19; 14/34; 38/77; 42; 45/29; 631/250/1619/554; 631/250/248; 64/60; 96/109; Apoptosis; Biochemistry; Biomedical and Life Sciences; CD4 antigen; CD8 antigen; Cell Biology; Cell Cycle Analysis; Cell differentiation; Cell lineage; Immune system; Life Sciences; Lymphocytes T; Major histocompatibility complex; Regulatory sequences; Runx3 protein; Stem Cells; T cell receptors; Thymocytes; Transgenic mice
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/s41418-020-0560-x

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 B 2 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.