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: England Nature Publishing Group 01.11.2020; Nature Publishing Group UK
• Subjects: CD4 antigen; CD8 antigen; Cell differentiation; Cell lineage; Immune system; Lymphocytes T; Major histocompatibility complex; Regulatory sequences; Runx3 protein; 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 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.