Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Swiss-Japanese Research Suggests Origins of Key Cells in the Thymus

31.05.2013
Medullary thymic epithelial cells (mTECs) allow the thymus to ensure that the body’s T cells are able to distinguish between potentially harmful foreign antigens and those that are produced by the body itself.

A Swiss-Japanese research team suggests that mTECs do not share a common progenitor with cortical-thymic TECs (cTECs) that produce T cells, but may actually evolve from them.

T-lymphocytes, or T cells, are a principal component of the body’s adaptive immune system. Together, these cells express a large repertoire of antigen specific receptors that recognise foreign material derived, for example, from pathogens and tumour cells. The generation of these antigen receptors occurs during T cell development in the thymus.

This constitutes, however, a random process that also includes the formation of antigen receptors which respond well to the body’s own proteins, so-called self-antigens. To prevent T cells bearing a self-reactive antigen receptor to exit from the thymus to the rest of the body where they may cause autoimmunity, a mechanism is in place that involves mTECs. These specialised thymic epithelial cells express most of the body’s self-antigens. T cells that recognise their specific antigen presented by mTECs will undergo a process of programmed cell death and are consequently deleted in the thymus.

Cross-Country Partnership

Very little is presently known about how cTECs and mTECs develop, or how they relate to each other. A Swiss-Japanese research team now reports that mTECs derive from cells that already express β5t, a proteasome subunit that is densely concentrated in cTECs and no other cell types, including mTECs themselves. This finding, which is published in the May 27-30, 2013 edition of PNAS, suggests that mTECs may evolve from cTECs. This finding has not only implications for how mTECs develop, but also how they may have evolved.

The research project was led in Switzerland by Prof. Georg Holländer, Professor of Paediatric Immunology at the University of Basel and Action Research Professor of Paediatrics at the University of Oxford. In Japan, the project was led by Prof. Yousuke Takahama of the Institute for Genome Research at the University of Tokushima, which initially discovered the β5t proteasome subunit. Dr. Izumi Ohigashi of the Institute for Genome Research at the University of Tokushima and Dr. Saulius Zuklys at the University Children’s Hospital of Basel serve as first authors.

Broad Potential

Professor Holländer believes that the benefits of a better understanding of the origins and functions of mTECs and cTECs extend well beyond basic research. The team’s findings suggest that evolutionary pressures have caused the body to check the quality of T cells that it produces. The T cell antigen receptor repertoire in evolutionary older species have a receptor, and did not require the body to implement quality control – but as the capacity developed to produce a seemingly infinite number of T cell antigen receptors the vital need to control their specificities has arisen. For this purpose the body may have “hijacked” existing cells, namely cTECs. Holländer also believes that the findings could inform attempts to reconstruct or develop in-vitro thymuses, which could in turn be used to help people who lack a normal thymus function because of inborn or acquired defects. “You can fix things if you know how they are formed in the first place,” he claims.

The research was supported by Grants-In-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology and the Japan Society for the Promotion of Science, and by a Strategic Japanese-Swiss Cooperative Program on Molecular Medical Research from the Japan Science and Technology Agency and the Federal Institute of Technology (ETH)-Zürich.

Original Citation

Izumi Ohigashi, Saulius Zuklys, Mie Sakata, Carlos E. Mayer, Saule Zhanybekova, Shigeo Murata, Keiji Tanaka, Georg Holländer, and Yousuke Takahama.
Aire-expressing thymic medullary epithelial cells originate from β5t-expressing progenitor cells.
Proceedings of the National Academy of Sciences of the United States of America, May 27-May 31, 2013. doi:10.1073/pnas.1301799110

Further Information

Professor Georg Holländer, Department of Biomedicine, University of Basel, Mattenstrasse 28 4058 Basel, Tel. +41 61 695 30 69, e-mail: georg-a.hollaender@unibas.ch

Professor Yousuke Takahama, Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima, Japan 770-8503 Tel. +81 88 633 9452, e-mail: takahama@genome.tokushima-u.ac.jp

Anne Zimmermann | Universität Basel
Further information:
http://www.pnas.org/content/early/2013/05/28/1301799110.abstract
http://biomedizin.unibas.ch/research/research-group-details/home/researchgroup/pediatric-immunology/

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>