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 Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>