Featured Research

from universities, journals, and other organizations

Immunologists find a molecule that puts the brakes on inflammation

Date:
September 28, 2012
Source:
University of Pennsylvania
Summary:
We couldn't live without our immune systems, always tuned to detect and eradicate invading pathogens and particles. But sometimes the immune response goes overboard, triggering autoimmune diseases like lupus, asthma or inflammatory bowel disease. A new study has now identified a crucial signaling molecule involved in counterbalancing the immune system attack.

We couldn't live without our immune systems, always tuned to detect and eradicate invading pathogens and particles. But sometimes the immune response goes overboard, triggering autoimmune diseases like lupus, asthma or inflammatory bowel disease.

Related Articles


A new study led by University of Pennsylvania researchers has now identified a crucial signaling molecule involved in counterbalancing the immune system attack.

"The immune response is like driving a car," said Christopher Hunter, professor and chair in the Department of Pathobiology in Penn's School of Veterinary Medicine. "You hit the accelerator and develop this response that's required to protect you from a pathogen, but, unless you have a brake to guide the response, then you'll just careen off the road and die because you can't control the speed of the response."

The research to characterize this immune system "brake" was led by Hunter and Aisling O'Hara Hall, a doctoral candidate in the Immunology Graduate Group. Additional Penn collaborators included scientists from the Penn Genome Frontiers Institute's Department of Biology and the Perelman School of Medicine's Department of Medicine. Researchers from Merck Research Laboratories, the National Institute of Allergy and Infectious Disease, Harvard Medical School and Janssen Research and Development also contributed to the work, which was published in the journal Immunity.

"Healthy people have these cells -- you have them, I have them -- that are called Tregs," or regulatory T cells, Hunter said. "If you don't have them you develop spontaneous inflammation and disease."

Different forms of regulatory T cells operate as the brakes on various kinds of inflammation, but, until now, scientists hadn't been certain of how these Tregs became specialized to do their particular jobs.

Hall, Hunter and colleagues decided to follow up on a molecule called IL-27. Scientists used to think IL-27 played a role in causing inflammation, but, in 2005, a team of Penn researchers, including Hunter, found the opposite; it was actually involved in suppressing inflammation. Thus, when mice that lack IL-27 are challenged with the parasite Toxoplasma gondii, they develop overwhelming inflammation.

"We never worked out how it did that, but it was a paradigm change at the time," Hunter said.

In the new study, the researchers delved deeper into IL-27's role. They found that exposing regulatory T cells to IL-27 promoted their ability to suppress a particular type of inflammation. The Penn-led team also demonstrated that they could rescue infected IL-27-deficient mice by giving them a transfusion of regulatory T cells. This finding suggests that IL-27 is required to produce the Treg cells that normally keep inflammatory responses in check during infection.

"Very surprisingly, we were able to show that the Tregs could ameliorate the pathology in this system," Hall said. "We don't think this is the only mechanism by which IL-27 limits immune pathology, but it sheds light on one mechanism by which it could be functioning."

Further experiments showed that Tregs express a different suite of genes in the presence of IL-27 as compared to another molecule that has been implicated in this process, interferon gamma, or IFN-γ. The researchers' findings indicate that the two molecules have division of labor when it comes to suppressing inflammation: IL-27 seems to be important in helping control inflammation at the site of inflammation, whereas IFN-γ appears more significant in the peripheral tissues.

"At the site of inflammation, where you're getting your pathology, that's where IL- 27 is important," Hall said.

With a new understanding of how IL-27 may cause a class of Tregs to become specialized inflammation fighters, researchers have a new target for ameliorating the unwanted inflammation associated with all kinds of autoimmune conditions.

"Now we have a molecular signature that may be relevant in inflammatory bowel disease, in multiple sclerosis, in colitis and Crohn's disease, in rheumatoid arthritis, in lupus," Hunter said.

Next on tap, the team plans to study IL-27 in the context of asthma, lupus and arthritis.

In addition to Hall and Hunter, the authors included Beena John, Claudia González Lombana, Gretchen Harms Pritchard, Jonathan S. Silver, Jason S. Stumhofer, Tajie H. Harris, Elia D. Tait Wojno, Sagie Wagage and Philip Scott of Penn Vet's Department of Pathobiology; Daniel P. Beiting, David S. Roos and Sara Cheery of the Penn Genome Frontiers Institute Department of Biology; Steven Reiner, formerly of the Penn Department of Medicine; Cristina M. Tato and Daniel Cua of Merck Research Laboratories; Yasmine Belkaid, Guillaume Oldenhove, Nicolas Bouladoux and John Grainger of the National Institute of Allergy and Infectious Disease; Laurence A. Turka of Harvard Medical School; and M. Merle Elloso of Janssen Research and Development.

The study was supported by the Commonwealth of Pennsylvania and the National Institutes of Health.


Story Source:

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


Journal Reference:

  1. Aisling O’Hara Hall, Daniel P. Beiting, Cristina Tato, Beena John, Guillaume Oldenhove, Claudia Gonzalez Lombana, Gretchen Harms Pritchard, Jonathan S. Silver, Nicolas Bouladoux, Jason S. Stumhofer, Tajie H. Harris, John Grainger, Elia D. Tait Wojno, Sagie Wagage, David S. Roos, Philip Scott, Laurence A. Turka, Sara Cherry, Steven L. Reiner, Daniel Cua, Yasmine Belkaid, M. Merle Elloso, Christopher A. Hunter. The Cytokines Interleukin 27 and Interferon-γ Promote Distinct Treg Cell Populations Required to Limit Infection-Induced Pathology. Immunity, 2012; 37 (3): 511 DOI: 10.1016/j.immuni.2012.06.014

Cite This Page:

University of Pennsylvania. "Immunologists find a molecule that puts the brakes on inflammation." ScienceDaily. ScienceDaily, 28 September 2012. <www.sciencedaily.com/releases/2012/09/120928125304.htm>.
University of Pennsylvania. (2012, September 28). Immunologists find a molecule that puts the brakes on inflammation. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2012/09/120928125304.htm
University of Pennsylvania. "Immunologists find a molecule that puts the brakes on inflammation." ScienceDaily. www.sciencedaily.com/releases/2012/09/120928125304.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) — It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) — More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) — In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) — A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
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