Featured Research

from universities, journals, and other organizations

New enzyme that acts as innate immunity sensor discovered

Date:
February 17, 2013
Source:
UT Southwestern Medical Center
Summary:
Two studies could lead to new treatments for lupus and other autoimmune diseases and strengthen current therapies for viral, bacterial, and parasitic infections.

Two studies by UT Southwestern researchers published in Science magazine could lead to new treatments for lupus and other autoimmune diseases. Shown left to right: Dr. Xiang Chen, research associate in molecular biology and HHMI research specialist I; Dr. Fenghe Du, research associate in molecular biology and a research specialist II at the HHMI; Dr. Lijun “Josh” Sun, assistant professor of molecular biology and HHMI research specialist III; senior author Dr. Zhijian “James” Chen, Dr. Chuo Chen, associate professor of biochemistry; Dr. Heping Shi, postdoctoral researcher of biochemistry; Not pictured: lead author of the cGAMP study Jiaxi Wu, a graduate student of molecular biology.
Credit: Image courtesy of UT Southwestern Medical Center

Two studies by researchers at UT Southwestern Medical Center could lead to new treatments for lupus and other autoimmune diseases and strengthen current therapies for viral, bacterial, and parasitic infections.

The studies identify a new enzyme that acts as a sensor of innate immunity -- the body's first line of defense against invaders -- and describe a novel cell signaling pathway. This pathway detects foreign DNA or even host DNA when it appears in a part of the cell where DNA should not be. In addition, the investigations show that the process enlists a naturally occurring compound in a class known to exist in bacteria but never before seen in humans or other multicellular organisms, said Dr. Zhijian "James" Chen.

Dr. Chen, professor of molecular biology and a Howard Hughes Medical Institute (HHMI) investigator at UTSW, is senior author of both studies available online and published in the February 15 print edition of Science. Although the immune-boosting response of DNA has long been recognized, the mechanism underlying that response remained a mystery, he said.

"In his 1908 Nobel acceptance speech, Ilya Mechnikov noted that surgeons in Europe treated patients with nucleic acids -- the building blocks of DNA -- to boost their patients' immune responses. That observation came four decades before scientists showed that DNA was the carrier of genetic information," Dr. Chen said.

Dr. Chen credits a uniquely biochemical approach for solving the longstanding puzzle. The approach used classical protein purification combined with a modern technology called quantitative mass spectrometry to identify the mysterious compound at the heart of the discovered process.

Under normal conditions, DNA is contained within membrane-bound structures such as the nucleus and mitochondria that are suspended within the cell's soupy interior, called the cytoplasm, he said. DNA in the cytoplasm is a danger signal that triggers immune responses, including production of type-1 interferons (IFN).

"Foreign DNA in the cytoplasm is a sign of attack by a virus, bacteria, or parasite," Dr. Chen said. "Host DNA that somehow leaks into the cytoplasm can trigger autoimmune conditions, like lupus, Sjogren's syndrome, and Aicardi-Goutiere's syndrome in humans."

In these studies, UTSW researchers identified a new sensor of innate immunity -- the enzyme cyclic GMP-AMP synthase (cGAS) -- that sounds a cellular alarm when it encounters DNA in the cytoplasm. After the enzyme detects and binds to the DNA, it catalyzes the formation of a compound called cyclic GMP-AMP (cGAMP), the compound never before seen in humans, Dr. Chen said.

The cGAMP functions as a second messenger that binds to an adaptor protein called STING, which activates a cell signaling cascade that in turn produces agents of inflammation: interferons and cytokines.

"Normally this pathway is important for immune defense against infections by microbial pathogens. However, when the immune system turns against host DNA, it can cause autoimmune diseases," Dr. Chen said. "Our discovery of cGAS as the DNA sensor provides an attractive target for the development of new drugs that might treat autoimmune diseases."

The studies were funded by the National Institutes of Health and by the HHMI.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal References:

  1. L. Sun, J. Wu, F. Du, X. Chen, Z. J. Chen. Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway. Science, 2012; 339 (6121): 786 DOI: 10.1126/science.1232458
  2. J. Wu, L. Sun, X. Chen, F. Du, H. Shi, C. Chen, Z. J. Chen. Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Science, 2012; 339 (6121): 826 DOI: 10.1126/science.1229963

Cite This Page:

UT Southwestern Medical Center. "New enzyme that acts as innate immunity sensor discovered." ScienceDaily. ScienceDaily, 17 February 2013. <www.sciencedaily.com/releases/2013/02/130217085033.htm>.
UT Southwestern Medical Center. (2013, February 17). New enzyme that acts as innate immunity sensor discovered. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2013/02/130217085033.htm
UT Southwestern Medical Center. "New enzyme that acts as innate immunity sensor discovered." ScienceDaily. www.sciencedaily.com/releases/2013/02/130217085033.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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