Navigation Links
New insights into how immune system fights atherosclerosis
Date:12/21/2012

New York, NY (December 21, 2012) A study led by Columbia University Medical Center (CUMC) researchers has found that an important branch of the immune system, in reaction to the development of atherosclerotic lesions, mounts a surprisingly robust anti-inflammatory T cell response that helps prevent the disease from progressing. The findings may help inform the design of anti-atherosclerosis vaccines and other therapies that can take advantage of this aspect of the immune system. The study was published today in the online edition of the Journal of Clinical Investigation.

When the body encounters viruses, bacteria, or other potential threats, dendritic cells the sentinels of the immune system are dispatched to take a sample of the pathogen and present it to T cells. This activates the production of pro-inflammatory effector T cells (which attack the pathogen) and anti-inflammatory regulatory T cells (which keep the pro-inflammatory response in check).

"Normally, the pro-inflammatory response dominates, and that is what people assumed to be the case in atherosclerosis," said study leader Ira Tabas, MD, PhD, the Richard J. Stock Professor, Department of Medicine, and professor of pathology & cell biology (in physiology and cellular biophysics) at CUMC. "However, we found that the T cell response to atherosclerosis is mostly anti-inflammatory."

The researchers, led by postdoctoral scientist Manikandan Subramanian, PhD, used mice whose dendritic cells lacked MYD88, a signaling protein that initiates the cells' maturation. Since immature dendritic cells cannot activate T cells, the elimination of MYD88 effectively disabled the production of both effector and regulatory T cells. The mice were also bred to lack the LDL receptor, leaving them prone to the development of atherosclerosis.

The net effect of these changes in the mice was to increase the size of atherosclerotic lesions. "What this means is that the dominant effect of dendritic cells in the setting of atherosclerosis is to promote the development of protective regulatory T cells," said Dr. Tabas.

Earlier studies had suggested just the opposite: that effector T cells dominate in response to atherosclerosis. "In those studies, researchers disabled dendritic cells at an earlier stage, creating all sorts of compensatory processes," said Dr. Tabas. "That's probably why they came to a different conclusion. In our model, we were able to knock out only the step involved in activating T cells, leaving everything else alone."

The researchers found that T regulatory cells act by suppressing pro-inflammatory effector T cells and macrophages, which was expected. They also identified a new mechanism that directly links regulatory-T-cell activation with protection from atherosclerosis. According to Dr. Tabas, regulatory T cells secrete TGF-beta (a cytokine, or signaling molecule), which suppresses MCP-1 (monocyte chemoattractant protein-1), a protein that recruits monocytes, a type of white blood cell.

"Now we have a specific mechanism that could explain the preclinical success of dendritic vaccines and that provides a new understanding of how these vaccines might be improved," said Dr. Tabas.


'/>"/>
Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert

Related biology news :

1. New insights into cloud formation
2. Research on flavanols and procyanidins provides new insights into how these phytonutrients may positively impact human health
3. Battle of the sexes offers evolutionary insights
4. Study provides new insights into structure of heart muscle fibers
5. Study offers new insights into the effects of stress on pregnancy
6. Cell biology -- new insights into the life of microtubules
7. Yak genome provides new insights into high altitude adaptation
8. Zebrafish provide insights into causes and treatment of human diseases
9. Feces fossils yield new insights into ancient diets and thrifty genes
10. Piglets in mazes provide insights into human cognitive development
11. The ENCODE Project publishes new genomic insights in special issue of Genome Research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... superior patient care by providing unparalleled technology to leaders of the medical imaging industry. ... recently added to the range of products distributed by Ampronix. Photo - ... ... ... ...
(Date:5/12/2016)... WearablesResearch.com , a brand of Troubadour ... from the Q1 wave of its quarterly wearables survey. ... receptivity to a program where they would receive discounts ... company. "We were surprised to see that ... LaColla , CEO of Troubadour Research, "primarily because there ...
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 ... of Infosys (NYSE: INFY ), and Samsung SDS, ... partnership that will provide end customers with a more ... payment services.      (Logo: http://photos.prnewswire.com/prnh/20130122/589162 ) ... financial services, but it also plays a fundamental part in ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... HOUSTON , June 23, 2016 ... agreement with the Cy-Fair Sports Association to serve ... of the agreement, Houston Methodist Willowbrook will provide ... education and connectivity with association coaches, volunteers, athletes ... partner with the Cy-Fair Sports Association and to ...
(Date:6/23/2016)... FRANCISCO , June 23, 2016   EpiBiome ... has secured $1 million in debt financing from Silicon ... ramp up automation and to advance its drug development ... its new facility. "SVB has been an ... beyond the services a traditional bank would provide," said ...
(Date:6/23/2016)... , June 23, 2016 Apellis Pharmaceuticals, ... 1 clinical trials of its complement C3 inhibitor, ... and multiple ascending dose studies designed to assess ... of subcutaneous injection in healthy adult volunteers. ... either as a single dose (ranging from 45 ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... exhibiting at the Pennsylvania Convention Center and will showcase its product’s latest features ... will also be presenting a scientific poster on Disrupting Clinical Trials in The ...
Breaking Biology Technology: