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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 ef
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Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert

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