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学術論文

Autoimmunity associated with chemically induced thymic dysplasia

MPS-Authors

Nagakubo,  Daisuke
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;
External Organizations;

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Swann,  Jeremy
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Birmelin,  Stefanie
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Boehm,  T.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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引用

Nagakubo, D., Swann, J., Birmelin, S., & Boehm, T. (2017). Autoimmunity associated with chemically induced thymic dysplasia. International Immunology, 29, 385-390. doi:10.1093/intimm/dxx048.


引用: https://hdl.handle.net/21.11116/0000-0000-C1F0-6
要旨
Thymopoiesis strictly depends on the function of the Foxn1 transcription factor that is expressed in the thymic epithelium. During embryonic development, initial expression of the Foxn1 gene is induced in the pharyngeal endoderm by mesenchyme-derived BMP4 signals. Here, by engineering a time-delayed feedback system of BMP inhibition in mouse embryos, we demonstrate that thymopoiesis irreversibly fails if Foxn1 gene expression does not occur during a defining time span in mid-gestation. We also reveal an epistatic interaction between the extent of BMP signalling and the gene dosage of Foxn1. Our findings illustrate the complexities of the early steps of thymopoiesis and indicate that sporadic forms of thymic hypoplasia in humans may result from the interaction of genes affecting the magnitude of BMP signalling and Foxn1 expression