Foxn1-β5t transcriptional axis controls CD8+ T-cell production in the thymus
| Autor: | Shigeo Murata, Mie Sakata, Jun Hamazaki, Immanuel Rode, Yousuke Takahama, Tomomi Nakayama, Keiji Tanaka, Izumi Ohigashi, Ryo Motosugi, Tatsuya Takemoto, Yasumasa Nishito, Muhammad Myn Uddin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Science education General Physics and Astronomy Mice Transgenic Organogenesis Thymus Gland CD8-Positive T-Lymphocytes Biology Genome Article General Biochemistry Genetics and Molecular Biology Tissue Culture Techniques Mice 03 medical and health sciences 0302 clinical medicine Transcription (biology) Animals Humans Point Mutation Cytotoxic T cell Regulatory Elements Transcriptional Transcription factor Cells Cultured Multidisciplinary integumentary system Point mutation FOXN1 Cell Differentiation Epithelial Cells Forkhead Transcription Factors hemic and immune systems General Chemistry Cell biology Mice Inbred C57BL HEK293 Cells 030104 developmental biology Gene Expression Regulation Mutagenesis Site-Directed Cancer research tissues CD8 030215 immunology |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-10 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Foxn1 is involved in thymic epithelial cell (TEC) and CD8+ T cell development. Here the authors show this development requires Foxn1 binding proximal to, and inducing transcription of, the gene encoding β5t in cortical TECs. |
| Databáze: | OpenAIRE |
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