Foxn1-β5t transcriptional axis controls CD8<sup>+</sup> T-cell production in the thymus.

Uddin, Muhammad Myn; Ohigashi, Izumi; Motosugi, Ryo; Nakayama, Tomomi; Sakata, Mie; Hamazaki, Jun; Nishito, Yasumasa; Rode, Immanuel et al. · Nat Commun · 2017

basic_science · Level V

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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<sup>+</sup> T cells. A point mutation in this genome element results in a defect in β5t expression and CD8<sup>+</sup> T-cell production in mice. The results reveal a Foxn1-β5t transcriptional axis that governs CD8<sup>+</sup> T-cell production in the thymus.

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