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 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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Acknowledgements
This work was supported by the National Research Foundation of Korea, funded by the Korea government through Grants NRF-2016R1A2B3013865 and Korea Mouse Phenotyping Project Grant NRF-2014M3A9D5A01073789 of the Ministry of Science, ICT and Future Planning through the National Research Foundation.
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Hwang, S., Lee, C., Park, K. et al. Twist2 promotes CD8+ T-cell differentiation by repressing ThPOK expression. Cell Death Differ 27, 3053–3064 (2020). https://doi.org/10.1038/s41418-020-0560-x
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DOI: https://doi.org/10.1038/s41418-020-0560-x
