Too much of a good thing: overactive immune cells trigger inflammation

Molecular model: A typical interaction between the A45T mutated SDHA gene (green) and the SDHB gene (blue). DBM

The immune system protects us from infections and tumors – a challenging task, not least because harming the body’s own healthy tissue must be avoided at the same time. However, rare genetic diseases lead to defects in the immune system known as primary immunodeficiency disorders (PID).

One consequence of such disorders is susceptibility to infections, yet certain tumors and non-infectious inflammation (autoimmune diseases) can also occur more frequently.

The researchers tested the hypothesis that the metabolic activity in the immune cells of PID patients can serve as a biomarker. They based this on the fact that cellular metabolism is a key regulator of the functioning of immune cells.

In the immune cells of a subset of the examined PID patients, a key metabolic process – cellular respiration – was indeed significantly increased. During cellular respiration, energy is generated in the mitochondria, the “powerhouses of the cell”.

Increased cellular respiration

On the basis of this discovery, the researchers were able to decode a new kind of disease mechanism, from the genetic defect via mitochondria and back to signal transduction to the nucleus.

The increased cellular respiration was triggered by the hyperactivity of a protein in the respiratory chain. This then signaled the cells to produce inflammatory mediators. With these findings, the researchers were able to successfully administer a targeted treatment approved for another indication.

The study was led by Professor Christoph Hess (Department of Biomedicine (DBM) of the University of Basel and University Hospital Basel, and CITIID, University of Cambridge) and Professor Mike Recher (DBM, University of Basel and University Hospital Basel).

“It is an example of how patient-based research can help to decode disease-causing molecular processes,” Christoph Hess says. This benefits patients, who may receive more targeted and effective medication with fewer side effects. Further, insights into fundamental biological processes gained from studying rare diseases can also enable new pathophysiological considerations relating to more common diseases.

Prof. Dr. Christoph Hess, University of Basel, Department of Biomedicine, Immunobiology, phone: +41 61 328 68 30, e-mail: chess@uhbs.ch

Anne-Valérie Burgener, Glenn R. Bantug et al.
SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1–Nrf2
Nature Immunology | DOI 10.1038/s41590-019-0482-2

Media Contact

Christoph Dieffenbacher Universität Basel

Further information:

http://www.unibas.ch

All news from this category: Life Sciences

Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to the Homepage

Comments (0)

Write comment

Latest posts

Seawater as an electrical cable !?

Wireless power transfers in the ocean For drones that can be stationed underwater for the adoption of ICT in mariculture. Associate professor Masaya Tamura, Kousuke Murai (who has completed the…

Rare quadruple-helix DNA found in living human cells with glowing probes

New probes allow scientists to see four-stranded DNA interacting with molecules inside living human cells, unravelling its role in cellular processes. DNA usually forms the classic double helix shape of…

A rift in the retina may help repair the optic nerve

In experiments in mouse tissues and human cells, Johns Hopkins Medicine researchers say they have found that removing a membrane that lines the back of the eye may improve the…

Partners & Sponsors

By continuing to use the site, you agree to the use of cookies. more information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close