Nav: Home

Mouse study points way to shut down harmful immune response in lupus

August 17, 2016

DURHAM, N.C. - Molecules that scavenge debris from dying cells appear to halt the cycle of chronic inflammation in lupus, while also enhancing the body's ability to combat flu, according to Duke Health studies in mice.

The molecules, called polymers, have commonly been used in gene-transfer experiments because they bind to the nucleic acid in DNA and RNA. When deployed directly in mice with lupus or an acute flu infection, the polymers home in on the DNA and RNA refuse from dying cells, halting the damaging immune attack.

"This debris left by dead cells can mistakenly signal to the body that there is an infection that warrants immune action, triggering the innate immune system," said Bruce A. Sullenger, Ph.D., director of the Duke Translational Research Institute. Sullenger is senior author of a study published online this week in the Proceedings of the National Academy of Sciences.

"By selectively targeting the source of the immune activation rather than shutting off the innate immune system downstream, these nucleic acid scavengers are able to limit pathological inflammation without compromising one's ability to fight a viral infection," Sullenger said.

Pathological inflammation, a major cause of illness and death around the world, is a hallmark of autoimmune diseases, including lupus and diabetes, as well as chronic conditions such as heart disease and some cancers. It also fuels the organ failure associated with severe infectious diseases such as Ebola or even flu.

Current therapies to treat pathological inflammation generally focus on quieting the overactive immune response, but in suppressing the immune system, patients are vulnerable to severe infections arising from other sources.

Intrigued by the ability of certain polymers to mop up DNA and RNA for gene transfer, Sullenger and colleagues tested the idea that these chemical compounds might also be effective targeting such nucleic acids as they arise in cell death.

"Essentially what you have in an autoimmune disease is a vicious cycle," said lead author Eda K. Holl, Ph.D., assistant professor in Duke's Department of Surgery. "Our goal was to break this cycle at its onset. What we saw in animals with lupus when we used these compounds was a dramatic reduction in inflammation, which gave the body a chance to heal."

Sullenger and Holl said the approach was further tested to see if it compromised the mice's ability to fight outside infections. When they exposed the treated mice to the influenza virus, the animals recovered from the illness even better than healthy mice infected with flu that had not undergone the treatment.

"This approach has the potential to treat a wide range of inflammatory conditions --from lupus to diabetes to even obesity," Sullenger said.

He said the research team is continuing studies in animal models and working to start a company to develop and commercialize the scavenger approach.
-end-
In addition to Sullenger and Holl, study authors from Duke include Kara L. Shumansky, Angela D. Burnette, Christopher J. Sample, and Elizabeth A. Ramsburg. They were joined by Luke B. Borst of N.C. State University.

The work received support from the National Institutes of Health (R56 AI093900, R01 HL06522, P01 HL11626, F32 DK094543) and the Coulter Foundation.

Duke University Medical Center

Related Immune System Articles:

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.