Featured Research

from universities, journals, and other organizations

Lupus erythematosus and sunlight induced DNA Crash

Date:
August 29, 2013
Source:
Universität Bonn
Summary:
Summer, sun and the sea – a dream vacation for most - can turn sour for those affected by lupus erythematosus. For them, absorption of the UV-light component in sunlight may cause florid inflammation and redness of the skin. Scientists have now discovered which signaling pathway of the innate immune system promotes autoimmune symptoms following sun-induced DNA damage.

Sunlight can damage DNA: Dr. Winfried Barchet (centre), and his co-workers at the Institute of Clinical Chemistry and Clinical Pharmacology visualize their findings using black tubing to represent the DNA double helix. Nadine Gehrke (on the far left), Christina Mertens (far right) and Thomas Zillinger (fourth from the right) share first authorship on the publication.
Credit: Anna-Maria Herzner/UKB

Summer, sun and the sea -- a dream vacation for most -- can turn sour for those affected by lupus erythematosus. For them, absorption of the UV-light component in sunlight may cause florid inflammation and redness of the skin. Scientists of the University Hospital Bonn, Germany have now discovered which signaling pathway of the innate immune system promotes autoimmune symptoms following sun-induced DNA damage. The results are now published online in the academic journal Immunity.

Lupus erythematosus (LE) is an autoimmune disorder in which the immune system erroneously attacks the body's own tissues. Where most people merely suffer sunburn, LE prone patients may develop severe redness and inflammation in sun-exposed skin. Immunologists of the University Hospital Bonn together with the Dermatologists Profs. Thomas Tüting and Jörg Wenzel have now discovered an immune mechanism that triggers LE skin lesions. "We have shown how the UV component of sunlight may cause DNA damage in cells, and in consequence lead to an alarm response from the innate immune system," reports Dr. Winfried Barchet, head of the Emmy Noether-research team "Immunorecognition of viral nucleic acids in the cytosol" at the Institute of Clinical Chemistry and Clinical Pharmacology at the university clinics of Bonn.

How DNA damage produces a false alarm

High-energy UV irradiation damages DNA in the nuclei of living cells that in consequence perish, and release the UV-altered DNA. In lupus patients this triggers a troublesome signaling cascade: "The innate immune system usually detects viruses via their nucleic acids. Here however, this state of emergency is declared erroneously due to the crash in the body's own DNA," says Dr. Barchet. The majority of the innate immune receptors that detect viral nucleic acids and in consequence activate inflammatory immune defense mechanisms are now known.

"For the induction of lupus symptoms, according to our data, the decisive role is played by the very recently discovered immune receptor cGAMP-Synthase (cGAS)," says Dr. Barchet. DNA released from dying cells is taken up by immune cells and then degraded by the enzyme TREX1. When the cellular DNA is UV damaged, however, TREX1 is ineffective according to the results of the Bonn researchers. Damaged DNA accumulates and activates the cGAS signaling pathway, thus ringing a false alarm for the immune system

The researchers were also able to support this concept with a mouse model in which a gene defect makes them prone to develop lupus-like autoimmune disease. When the immunologists injected DNA damaged by UV-light into the skin, the animals locally developed typical lupus symptoms: skin swelling and inflammation, infiltration of immune cells that eventually attacked skin tissue. Control injections of intact DNA, in contrast, did not cause such skin alterations.

"These signaling events may explain why lupus patients are prone to UV-light induced skin lesions," says the researcher. This study is the first to implicate the cGAS receptor in this autoimmune disorder. Dr. Barchet envisions potential targets for novel lupus therapies: "With a suitable inhibitor of the cGAS signaling cascade, it may become possible to suppress sunlight induced symptoms of the disease. On the other hand, it is puzzling why the immune system has evolved and maintained such a potentially harmful mechanism. We believe that in healthy individuals it must have an important function in the defense against pathogens that we would very much like to understand as well," says Dr. Barchet.


Story Source:

The above story is based on materials provided by Universität Bonn. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nadine Gehrke, Christina Mertens, Thomas Zillinger, Jörg Wenzel, Tobias Bald, Sabine Zahn, Thomas Tüting, Gunther Hartmann, Winfried Barchet. Oxidative Damage of DNA Confers Resistance to Cytosolic Nuclease TREX1 Degradation and Potentiates STING-Dependent Immune Sensing. Immunity, 2013; DOI: 10.1016/j.immuni.2013.08.004

Cite This Page:

Universität Bonn. "Lupus erythematosus and sunlight induced DNA Crash." ScienceDaily. ScienceDaily, 29 August 2013. <www.sciencedaily.com/releases/2013/08/130829123530.htm>.
Universität Bonn. (2013, August 29). Lupus erythematosus and sunlight induced DNA Crash. ScienceDaily. Retrieved August 20, 2014 from www.sciencedaily.com/releases/2013/08/130829123530.htm
Universität Bonn. "Lupus erythematosus and sunlight induced DNA Crash." ScienceDaily. www.sciencedaily.com/releases/2013/08/130829123530.htm (accessed August 20, 2014).

Share This




More Health & Medicine News

Wednesday, August 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) — Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) — Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
Powered by NewsLook.com
American Ebola Patient Apparently Improving, Outbreak Is Not

American Ebola Patient Apparently Improving, Outbreak Is Not

Newsy (Aug. 19, 2014) — Nancy Writebol, an American missionary who contracted Ebola, is apparently getting better, according to her husband. The outbreak, however, is not. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins