Foxn1-β5t transcriptional axis controls CD8+T-cell production in the thymus.
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.
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan.
Muhammad Myn
MM
Uddin
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan.
Izumi
I
Ohigashi
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Ryo
R
Motosugi
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Tomomi
T
Nakayama
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan.
Mie
M
Sakata
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Jun
J
Hamazaki
Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Yasumasa
Y
Nishito
Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany.
Immanuel
I
Rode
Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Keiji
K
Tanaka
Laboratory for Embryology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan.
Tatsuya
T
Takemoto
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Shigeo
0000-0002-3177-3503
S
Murata
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan.
Yousuke
Y
Takahama
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*; D046509:Tissue Culture Techniques
D051858:Forkhead Transcription Factors; C090140:Whn protein; D046988:Proteasome Endopeptidase Complex; C520309:proteasome subunit beta5t, mouse