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Atherosclerosis: How immune cells migrate into plaques

25 Feb 2025

CD8+ T cells accumulate in atherosclerotic plaques. LMU researchers identify a crucial signaling pathway in this process - with therapeutic potential.

Atherosclerosis is the most common cause of life-threatening cardiovascular diseases. The disease is characterized by chronic inflammation of the inner walls of blood vessels and atherosclerotic plaques. A team led by Johan Duchêne and Remco Megens from the Institute for Prophylaxis and Epidemiology of Circulatory Diseases has now identified a signaling pathway that is involved in the recruitment of a specific subset of immune cells, the so-called CD8+ T cells, into the plaques - with possible implications for new therapeutic approaches.

For a long time, macrophages and foam cells were considered the main players in the development of plaques. However, more recent studies have focused on other cells of the immune system - so-called CD8+ T cells - as these have been shown to be the most common cells of the hematopoietic system in human atherosclerotic plaques. "To better understand their role, it is important to know how they are recruited to atherosclerotic plaques," says Laura Parma, first author of the study.

Deciphering the decisive signaling pathway

To answer this question, the scientists cultivated human atherosclerotic plaques together with CD8+ cells from the same patient in a specially developed three-dimensional tissue culture model. This showed that the added CD8+ T cells were mainly found in the vicinity of newly formed blood vessels within the plaques. Further analyses using single-cell RNA sequencing and 3D microscopy revealed that the endothelial cells of these vessels express large amounts of the messenger substance CXCL12.

The researchers therefore subsequently investigated whether CXCL12 is involved in the recruitment of CD8+ cells by blocking the corresponding receptor (CXCR4) for this messenger substance in the T cells. "Indeed, this led to a significant reduction in CD8+ T cell migration in atherosclerotic plaques," says Duchêne, "suggesting that the CXCL12-CXCR4 signaling pathway plays a key role in this process."

"These results provide new starting points for potential therapeutic strategies to influence immune cell infiltration in atherosclerotic plaques and could contribute to the development of new treatment options for cardiovascular diseases in the long term," concludes Megens.