Featured Research

from universities, journals, and other organizations

New insights into how immune system fights atherosclerosis

Date:
December 21, 2012
Source:
Columbia University Medical Center
Summary:
A new study 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.

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 December 21 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.


Story Source:

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


Journal Reference:

  1. Manikandan Subramanian, Edward Thorp, Goran K. Hansson, Ira Tabas. Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs. Journal of Clinical Investigation, 2012; DOI: 10.1172/JCI64617

Cite This Page:

Columbia University Medical Center. "New insights into how immune system fights atherosclerosis." ScienceDaily. ScienceDaily, 21 December 2012. <www.sciencedaily.com/releases/2012/12/121221131301.htm>.
Columbia University Medical Center. (2012, December 21). New insights into how immune system fights atherosclerosis. ScienceDaily. Retrieved April 21, 2014 from www.sciencedaily.com/releases/2012/12/121221131301.htm
Columbia University Medical Center. "New insights into how immune system fights atherosclerosis." ScienceDaily. www.sciencedaily.com/releases/2012/12/121221131301.htm (accessed April 21, 2014).

Share This



More Health & Medicine News

Monday, April 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Breakfast Foods Are Getting Pricier

Breakfast Foods Are Getting Pricier

AP (Apr. 21, 2014) Breakfast is now being served with a side of sticker shock. The cost of morning staples like bacon, coffee and orange juice is on the rise because of global supply problems. (April 21) Video provided by AP
Powered by NewsLook.com
Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
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:
from the past week

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