A switch for autoimmunity

October 13, 2017 by Meredith Jackson, Vanderbilt University

When a virus or bacteria comes calling, protein "sensors" in your cells can detect the invader's DNA and activate inflammatory responses to prevent infection. One such sensor is cGAS (cyclic GMP-AMP synthase).

Normally, cGAS is an asset – something you definitely want to be working for you. However, abnormal responses to intracellular DNA can lead to hyper-inflammatory or autoimmune disorders such as lupus. Turning cGAS off may actually help treat this disease.

Manuel Ascano Jr., Ph.D., and colleagues now report the discovery of a class of compounds that can inhibit cGAS. One "chemically improved" compound, RU.521, showed potent and selective inhibition of cGAS activity and lowered inflammatory signaling molecules in immune cells in a mouse model of an autoimmune disease.

Reporting Sept. 29 in the journal Nature Communications, the researchers concluded that RU.521 will help scientists learn more about the biological roles of cGAS and as a "molecular scaffold" may pave the way for development of future therapies for .

Explore further: Researchers identify tactic Dengue virus uses to delay triggering immune response

More information: Jessica Vincent et al. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice, Nature Communications (2017). DOI: 10.1038/s41467-017-00833-9

Related Stories

Researchers identify tactic Dengue virus uses to delay triggering immune response

April 18, 2017
For the human body to mount an immune response to a viral infection, host cells must identify the viral invader and trigger a signaling pathway. This signal then prompts the immune system to attack and subdue the pathogen. ...

Cell senescence is regulated by innate DNA sensing

July 31, 2017
Cells in the body or in cultures eventually stop replicating. This phenomenon is called "senescence" and is triggered by shortening of telomeres, oxidative stress or genetic damage to the cells, either acute or simply due ...

Researchers identify an enzyme as a major culprit of autoimmune diseases

October 27, 2015
Activating an enzyme that sounds an alarm for the body's innate immune system causes two lethal autoimmune diseases in mice, while inhibiting the same enzyme rescues them, UT Southwestern Medical Center researchers report.

MicroRNA helps cancer evade immune system

September 18, 2017
The immune system automatically destroys dysfunctional cells such as cancer cells, but cancerous tumors often survive nonetheless. A new study by Salk scientists shows one method by which fast-growing tumors evade anti-tumor ...

Researchers discover immune system's 'Trojan Horse'

July 31, 2015
Oxford University researchers have found that human cells use viruses as Trojan horses, transporting a messenger that encourages the immune system to fight the very virus that carries it. The discovery could have implications ...

DNA sensor plays critical role in cancer immunotherapy via response to unexpected DNA form

August 24, 2017
UT Southwestern Medical Center researchers report for the first time that tumors stressed by cancer immunotherapy release their mitochondrial DNA into nearby immune cells, triggering a host alert system.

Recommended for you

New study shows how gut immune cells are kept in control

June 22, 2018
Every day, the human gut works on a fine-tuned balance that ensures the retention of essential nutrients while preventing infection by potential armful microbes. Contributing to this surveillance system is a specialised group ...

Human immune 'trigger' map paves way for better treatments

June 21, 2018
A discovery about how human cells are 'triggered' to undergo an inflammatory type of cell death could have implications for treating cancer, stroke and tissue injury, and immune disorders.

Our intestinal microbiome influences metabolism—through the immune system

June 21, 2018
Research tells us that the commensal or "good" bacteria that inhabit our intestines help to regulate our metabolism. A new study in fruit flies, published June 21 in Cell Metabolism, shows one surprising way they do this.

Fetal T cells are first responders to infection in adults

June 20, 2018
Cornell University researchers have discovered there is a division of labor among immune cells that fight invading pathogens in the body.

How a thieving transcription factor dominates the genome

June 20, 2018
One powerful DNA-binding protein, the transcription factor PU.1, steals away other transcription factors and recruits them for its own purposes, effectively dominating gene regulation in developing immune cells, according ...

Severe stress may send immune system into overdrive

June 19, 2018
(HealthDay)—Trauma or intense stress may up your odds of developing an autoimmune disease, a new study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.