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The ‘Node’ Not Taken: Human lymph node biopsies as a window to the immune response in cardiovascular disease

Atherosclerosis, or the hardening and narrowing of arteries, is the number one cause of death worldwide and usually manifests as a heart attack or stroke. The immune system plays a major role in the development and progression of this disease. Immune cells respond to chemical signals emanating from the arteries, which engages system-wide chronic inflammation and causes an array of cells to infiltrate artery walls. Then, over many years, cell invasion of arteries leads to plaque formation and usually coincides with a host of other inflammatory diseases, including diabetes.

In human studies, the majority of atherosclerosis research is performed on blood samples and a minority of research on carotid artery plaque. However, no studies to date have explored the involvement of lymphatic organs, such as lymph nodes. During a typical immune response, scout cells at the site of inflammation or infection report back to the nearest lymph nodes to notify and activate specialized fighter immune cells. These fighter cells quickly undergo changes and are dispatched from the lymph node to enter battle at the site of inflammation. This response is highly efficient at clearing a typical infection, however, in atherosclerosis, your own arteries are the target. Luckily, our immune system has adapted a natural response to limit hurting ourselves. This peacekeeping cell that prevents self-harm is found circulating in the blood and is a special type of T cell, called a regulatory T cell.

Within the plaque, however, a tumultuous environment rages on. Our lab has successfully described most of the immune cells that are involved in this seemingly unrestrained atmosphere. Interestingly, we noticed that the cells best suited to defend against atherosclerosis are the regulatory T cells, which are mostly present in the blood, not plaque, and disappear over the course of disease. We think by training these cells, such as through vaccination, we could prevent or even reverse atherosclerosis.

The regulatory T cells originate in the lymph node, where they are trained and dispatched to ultimately suppress inflammation. Here we embark on the road not taken, to identify their targets and understand their dynamics in lymph nodes during atherosclerosis in order to progress towards viable therapies, including vaccination.