Researchers at the universities of Basel and Oxford have for the first time identified all genes regulated by the protein Foxn1. The results show that Foxn1 not only plays a crucial role in development of the thymus in the embryo, but it also regulates vital functions in the developed, postnatal organ. The decryption of the protein’s functions is important in the understanding and treatment of autoimmune diseases, vaccination responses in old age and defense against tumor cells. The study was published in the journal Nature Immunology.
Like all vertebrate animals, humans use T cells in immune defense in order to protect the body against infections and malignant cells. Immune cells mature in the thymus, an organ located between the sternum and heart, during the embryonic stage, but they reach full functionality only when they interact with thymus epithelial cells – the teachers of the T cell, so to speak. The thymus begins to age from the second year of life.
More than 20 years ago, researchers discovered that the protein Foxn1 plays an important role in the development and differentiation of thymic epithelial cells. But it remained unclear which target genes controlled by Foxn1 were responsible for the formation and functions of the specialized epithelial cells. It was also unclear what Foxn1 actually did after development of the thymus in the embryo.
Healthy adults do not directly depend on the work of the thymus; however, the organ’s function becomes important again once the body requires new T cells – for example, after chemotherapy or a bone marrow transplant. To prevent the patient from remaining highly immune-deficient, thymic epithelial cells have to instruct the generation of new T cells.
Genome map of the regulator Foxn1
Researchers at the University of Basel, the University Children’s Hospital Basel and the University of Oxford have now succeeded in identifying in thymic epithelial cells the DNA sequence bound by the protein. The team, led by Professor Georg A. Holländer, was able to create a genome-wide map that lists all the DNA segments regulated by Foxn1. It emerged that Foxn1 controls almost all functions of the thymus, in whole or in part. “The protein is not only involved in the development of the organ, it also remains essential for its function throughout a person's life,” says the immunologist.
The research results provide important insights into the regulatory functions of thymic epithelial cells and could contribute to the development of new strategies for maintaining the thymus function in old age. “Now that we know exactly what Foxn1 does, we can think about how we can keep the thymus functioning in old age to reduce the risk of autoimmune disease and increased susceptibility to infections and tumors,” says Holländer.
Saulius Žuklys, Adam Handel, Saule Zhanybekova, Fatima Govani, Marcel Keller, Stefano Maio, Carlos E. Mayer, Hong Ying Teh, Katrin Hafen, Giuseppe Gallone, Thomas Barthlott, Chris P. Ponting and Georg A. Holländer
Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells
Nature Immunology (2016), doi: 10.1038/ni.3537
Georg A. Holländer, University of Basel, Department of Biomedicine/University Children’s Hospital Basel, Tel. +41 61 270 50 69, email: email@example.com
Saulius Zuklys, University of Basel, Department of Biomedicine/University Children’s Hospital Basel, Tel. +41 61 207 50 68, email: firstname.lastname@example.org
Olivia Poisson | Universität Basel
The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology
Colorectal cancer risk factors decrypted
16.07.2018 | Max-Planck-Institut für Stoffwechselforschung
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Transportation and Logistics
16.07.2018 | Agricultural and Forestry Science