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Foxn1-?5t transcriptional axis controls CD8+ T-cell production in the thymus.

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 ?5t, 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 ?5t expression and CD8+ T-cell production in mice. The results reveal a Foxn1-?5t transcriptional axis that governs CD8+ T-cell production in the thymus.

SUBMITTER: Uddin MM

PROVIDER: S-EPMC5309848 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Uddin Muhammad Myn MM Ohigashi Izumi I Motosugi Ryo R Nakayama Tomomi T Sakata Mie M Hamazaki Jun J Nishito Yasumasa Y Rode Immanuel I Tanaka Keiji K Takemoto Tatsuya T Murata Shigeo S Takahama Yousuke Y

Nature communications 20170208

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+</ ...[more]

PMID: 28176764

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