Foxn1-β5t transcriptional axis controls CD8+ T-cell production in the thymus

Muhammad Myn Uddin, Izumi Ohigashi, Ryo Motosugi, Tomomi Nakayama, Mie Sakata, Jun Hamazaki, Yasumasa Nishito, Immanuel Rode, Keiji Tanaka, Tatsuya Takemoto, Shigeo Murata () and Yousuke Takahama ()
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Muhammad Myn Uddin: Institute of Advanced Medical Sciences, University of Tokushima
Izumi Ohigashi: Institute of Advanced Medical Sciences, University of Tokushima
Ryo Motosugi: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo
Tomomi Nakayama: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo
Mie Sakata: Institute of Advanced Medical Sciences, University of Tokushima
Jun Hamazaki: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo
Yasumasa Nishito: Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science
Immanuel Rode: German Cancer Research Center
Keiji Tanaka: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science
Tatsuya Takemoto: Laboratory for Embryology, Institute of Advanced Medical Sciences, University of Tokushima
Shigeo Murata: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo
Yousuke Takahama: Institute of Advanced Medical Sciences, University of Tokushima

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract The thymus is an organ that produces functionally competent T cells that protect us from pathogens and malignancies. Foxn1 is a transcription factor that is essential for thymus organogenesis; however, the direct target for Foxn1 to actuate thymic T-cell production is unknown. Here we show that a Foxn1-binding cis-regulatory element promotes the transcription of β5t, which has an essential role in cortical thymic epithelial cells to induce positive selection of functionally competent CD8+ T cells. A point mutation in this genome element results in a defect in β5t expression and CD8+ T-cell production in mice. The results reveal a Foxn1-β5t transcriptional axis that governs CD8+ T-cell production in the thymus.

Date: 2017
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DOI: 10.1038/ncomms14419

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