Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The positive and negative role of LRH-1 during inflammation

25.07.2019

The research group around Professor Thomas Brunner at the University of Konstanz discovers the role that the LRH-1 protein plays in the immune system – Inhibiting this protein could help treat inflammatory diseases

Immune cells prevent bacteria, parasites or viruses from entering the body when, for example, the intestinal epithelium is injured. They respond with restricted inflammatory reactions, which are controlled via various processes in the healthy organism. If an organism suffers from Crohn’s disease, for example, the immune cells are continuously activated.


Detection of immune cells using specific antibodies in tissue sections of the spleen of wild type animals (left panel) and mice with T cell-specific deletion of LRH-1 (right panel). (Green: T lymphocytes, blue: B lymphozytes, red: macrophages).

Copyright: Thomas Brunner

The research group led by Professor Thomas Brunner at the University of Konstanz has demonstrated that the transcription factor LRH-1 plays a key role in immune cells. That this protein can actually be found in so-called T cells was already confirmed by his team several years ago.

The researchers in Konstanz were now able to show that the transcription factor is responsible for ensuring that an organism’s immune defence functions properly. If it is not present, no immune response is activated.

The researchers view this research result as an opportunity to develop therapeutic approaches or drugs that will control the damaging immune response by inhibiting LRH-1, as in Crohn’s disease or liver diseases.

A transcription factor is a protein that ensures that a gene is transcribed and a corresponding gene product is generated. It regulates the so-called gene expression process, which puts the gene’s information into effect. The transcription factor LRH-1 is particularly common in the intestine and liver.

The elimination of LRH-1 in the epithelial cells of these organs has little effect on them, though. However, the biologists found that the T cells, which are crucial for the immune response, hardly divide when LRH-1 is eliminated. With fatal consequences:

T cells have receptors that recognize specific foreign substances. A large number of them are needed to control pathogens such as viruses, which multiply rapidly after infiltrating the body. To fight these viruses, the T cells can usually divide very quickly – even faster than cancer cells – but in a more controlled manner.

“Without the LRH-1 transcription factor, it is practically impossible to trigger immune responses. As a result, the body can no longer protect itself against pathogens”, explains Thomas Brunner.

That is the negative aspect. On the positive side, however, this inhibition of the immune cell expansion can be used to treat inflammatory diseases such as Crohn’s disease or hepatitis. In the process of continuously fighting either harmless bacteria or viruses, the immune system’s permanent response actually damages the organs.

The overall aim is to shut down this out-of-control immune response. In fact, a pharmacological inhibitor that can specifically switch off the LRH-1 transcription factor activity already exists. A test has demonstrated that it actually blocks the T cells, thereby reducing the T cell mediated diseases.

Thomas Brunner and his team confirmed that the inhibition of LRH-1 yielded the hoped for results. “In order to test whether or not the inhibitor really works, we administered it to treat experimentally induced hepatitis. It did work. The damage was reduced”.

Facts:
- The research group around Professor Thomas Brunner at the University of Konstanz discovers the role that the LRH-1 protein plays in the immune system
- Inhibiting this protein could help treat inflammatory diseases
- Original publication: C. Seitz; J. Huang; A.-L. Geiselhöringer; P. Galbani-Bianchi; S. Michalek; T.S. Phan; C. Reinhold; L. Dietrich; C. Schmidt; N. Corazza; E. Delgado; T. Schnalzger; K. Schoonjans; T. Brunner: The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions. Science Advances, 17 July 2019: Vol. 5, no. 7, eaav9732. DOI: https://doi.org/10.1126/sciadv.aav9732
- On the discovery of LRH-1 in immune cells: https://www.ncbi.nlm.nih.gov/pubmed/28406481
- The project was funded by the German Research Foundation (DFG).

Note to editors:
You can download a photo here: https://cms.uni-konstanz.de/fileadmin/pi/fileserver/2019/Bilder/die_positive_und...

Caption: Detection of immune cells using specific antibodies in tissue sections of the spleen of wild type animals (left panel) and mice with T cell-specific deletion of LRH-1 (right panel). (Green: T lymphocytes, blue: B lymphozytes, red: macrophages).
Copyright: Thomas Brunner

Contact:
University of Konstanz
Communications and Marketing
Phone: +49 7531 88-3603
Email: kum@uni-konstanz.de

- uni.kn/en

Julia Wandt | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht First SARS-CoV-2 genomes in Austria openly available
03.04.2020 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

nachricht Do urban fish exhibit impaired sleep? Light pollution suppresses melatonin production in European perch
03.04.2020 | Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Harnessing the rain for hydrovoltaics

Drops of water falling on or sliding over surfaces may leave behind traces of electrical charge, causing the drops to charge themselves. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz have now begun a detailed investigation into this phenomenon that accompanies us in every-day life. They developed a method to quantify the charge generation and additionally created a theoretical model to aid understanding. According to the scientists, the observed effect could be a source of generated power and an important building block for understanding frictional electricity.

Water drops sliding over non-conducting surfaces can be found everywhere in our lives: From the dripping of a coffee machine, to a rinse in the shower, to an...

Im Focus: A sensational discovery: Traces of rainforests in West Antarctica

90 million-year-old forest soil provides unexpected evidence for exceptionally warm climate near the South Pole in the Cretaceous

An international team of researchers led by geoscientists from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now...

Im Focus: Blocking the Iron Transport Could Stop Tuberculosis

The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply. When the iron transport into the bacteria is inhibited, the pathogen can no longer grow. This opens novel ways to develop targeted tuberculosis drugs.

One of the most devastating pathogens that lives inside human cells is Mycobacterium tuberculosis, the bacillus that causes tuberculosis. According to the...

Im Focus: Physicist from Hannover Develops New Photon Source for Tap-proof Communication

An international team with the participation of Prof. Dr. Michael Kues from the Cluster of Excellence PhoenixD at Leibniz University Hannover has developed a new method for generating quantum-entangled photons in a spectral range of light that was previously inaccessible. The discovery can make the encryption of satellite-based communications much more secure in the future.

A 15-member research team from the UK, Germany and Japan has developed a new method for generating and detecting quantum-entangled photons at a wavelength of...

Im Focus: Junior scientists at the University of Rostock invent a funnel for light

Together with their colleagues from the University of Würzburg, physicists from the group of Professor Alexander Szameit at the University of Rostock have devised a “funnel” for photons. Their discovery was recently published in the renowned journal Science and holds great promise for novel ultra-sensitive detectors as well as innovative applications in telecommunications and information processing.

The quantum-optical properties of light and its interaction with matter has fascinated the Rostock professor Alexander Szameit since College.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

13th AKL – International Laser Technology Congress: May 4–6, 2022 in Aachen – Laser Technology Live already this year!

02.04.2020 | Event News

“4th Hybrid Materials and Structures 2020” takes place over the internet

26.03.2020 | Event News

Most significant international Learning Analytics conference will take place – fully online

23.03.2020 | Event News

 
Latest News

Capturing 3D microstructures in real time

03.04.2020 | Materials Sciences

First SARS-CoV-2 genomes in Austria openly available

03.04.2020 | Life Sciences

Do urban fish exhibit impaired sleep? Light pollution suppresses melatonin production in European perch

03.04.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>