New signaling pathway unveils atherosclerosis insights

Atherosclerosis is a disease that causes inflammation in the inner walls of blood vessels, leading to various heart conditions. Dendritic cells, which find foreign substances in the body, play a crucial role. They release a protein called CCL17 that affects the activity of T cells, which are responsible for fighting infections. 

Unfortunately, high levels of CCL17 can also cause heart problems. People with heart issues often have more CCL17. Scientists are trying to figure out how CCL17 from dendritic cells controls T cells, but they have yet to understand it fully.

A recent study in Nature Cardiovascular Research has revealed crucial details about signaling pathways in atherosclerosis. A lead author, Professor Christian Weber, explains that their previous research showed that blocking CCL17 helps slow atherosclerosis. 

The study found that a specific receptor is critical to T cell recruitment and functions. The body remains vulnerable to CCL17’s harmful effects without this receptor, as seen in a mouse study. Surprisingly, silencing this receptor did not have the same impact as blocking CCL17, suggesting there might be more to the story.

Weber’s colleague and first author, Professor Yvonne Döring explains, “These T cells would no longer be able to tackle the vascular inflammations. By targeting and inhibiting individual receptors of the investigated signaling pathway during their experiments, the authors showed that this mechanism plays a decisive role in the adverse effects of CCL17. “

Weber believes this is a significant step in understanding inflammatory diseases. The identified reaction pathway could be a crucial starting point for various treatments in chronic inflammatory conditions.

In conclusion, the discovery of this new signaling pathway represents a crucial advancement in understanding atherosclerosis. Unraveling the complexities of these molecular mechanisms provides a foundation for further research and potential therapeutic interventions in the ongoing battle against cardiovascular diseases.

Journal reference:

Döring, Y., van der Vorst, E.P.C., Yan, Y. et al. Identification of a non-canonical chemokine-receptor pathway suppressing regulatory T cells to drive atherosclerosis. Nature Cardiovascular Research. DOI: 10.1038/s44161-023-00413-9.

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