A group of researchers supervised by associate professor Dr. Alma Zernecke at Würzburg University, together with a team led by life scientist Dr. Yvonne Döring at LMU, has now shown how pDCs promote the development of atherosclerosis. "This could be the reason why patients with autoimmune diseases like psoriasis or systemic lupus erythematodes (SLE) develop atherosclerosis more frequently", Zernecke explains. "Indeed, both disorders feature overactive pDCs." pDCs respond to DNA released from damaged and dying cells by secreting interferon proteins which stimulate the immune reactions against some of the body's own proteins - a reaction typical for autoimmune diseases.
The new study shows that stimulation of pDCs by a specific DNA-protein contributes to the progression of atherosclerosis. The findings may entail new treatment strategies for an entire spectrum of conditions that are associated with chronic inflammatory reactions.
Using laboratory mice as an experimental model, the researchers were able to show that pDCs contribute to early steps in the formation of athersclerotic lesions in the blood vessels. Stimulation of pDCs causes them to secrete large amounts of interferons, proteins that strongly stimulate inflammatory processes. The protein that induces the release of interferons is produced by immune cells that accumulate specifically at sites of inflammation, and mice that are unable to produce this protein also have fewer plaques. Furthermore, stimulation of pDCs leads to an increase in the numbers of macrophages present in plaques. Macrophages normally act as a clean-up crew, removing cell debris and fatty deposits by ingesting them. However, they can also "overindulge", taking in more fat than they can digest. When this happens, they turn into so-called foam cells that promote rather than combat atherosclerosis.
According to this model, the stimulation of pDCs provides the link between atherosclerosis and autoimmune diseases. (© Ludwig Maximilians University Munich)