A study conducted by researchers at the Ludwig-Maximilians-Universität (LMU) Munich and the Würzburg University have found that dendritic cells influence the process of atherosclerosis by disrupting a mechanism that generally performs the role of a brake in the reactions of the immune system.
People in the western countries are prone to atherosclerosis, a leading cause of death in the western world. The condition, caused by the chronic inflammation of the blood vessel wall, supports the development of fibrous plaques, which in turn, raises the risk of heart attacks and strokes.
The inflammatory reaction persists due to loss of control over immune activities. The newly discovered dendritic cells are believed to activate other classes of immune cells. Researchers have suggested that these dendritic cells release a signal molecule called chemokine CCL17, which works by inhibiting a feedback mechanism that generally checks the immune reactions. This in turn, makes the inflammatory response chronic.
The research has also been able to recognize an antidote to the signal molecule. They claimed that they were able to stop the progression of atherosclerosis by deploying an antibody raised against the single molecule. In simple terms, this antidote can serve as the basis for the development of therapeutic strategies.
So how do the dendritic cells stimulate atherosclerosis? Atherosclerosis plaques, caused by lipid accumulation beneath the inner lining of the blood vessel, can result in a chronic inflammatory response. Immune cells move to the affected site and release signaling molecules, which in turn, attract other immune cells. These cells support plaque formation. These plaques serve as extra signals and the inflammation begins to become uncontrolled. Blood flow is obstructed.
The dendritic cells determine the targets against which the immune system directs its reactions. The dendritic cells activate the T cells, a type of immune cells. Professor Weber, who led the study on behalf of Ludwig-Maximilians-Universität (LMU) Munich, explained, "We were particularly interested in learning more about the role of the chemokine CCL17 - a signal protein that is specifically synthesized by mature dendritic cells - in the activation of T cells and in regulating T cell homeostasis."
Researchers made use of a transgenic mouse strain for the study. In this case, the researchers replaced the gene for CCL17 by a DNA sequence that encoded the genetic information for the GFP, Green Fluorescent Protein. The fluorescence of the protein allowed researchers to locate the CCL17 producing cells.
This approach also allowed the researchers to note the intrusion and the accumulation of the dendritic cells in the plaques and their interaction with the T cells. "The results of these investigations led us to conclude that CCL17 drives atherosclerosis by inhibiting an important regulatory circuit that acts to restrain the immune response," Professor Weber concluded on the findings of the study.
