New findings confirm that atherosclerosis is an autoimmune T-cell disease

Researchers from Germany, the United States and China carried out an experiment with mice and human cells, and detected that some types of T cells target the arterial wall

Atherosclerosis is a prototypical chronic inflammatory disease of the arteries. Its pathological hallmark is atherosclerotic plaque inside the arteries. When plaques rupture, they cause heart attacks or strokes. Major innate immune cells have been identified as involved in atherosclerosis.

In addition, various subtypes of T cells promote or attenuate the disease, according to research done in mice.

However, the central questions of T-cell immunity in atherosclerosis remain unanswered: in particular, it is not yet known whether atherosclerosis-associated T-cell responses take place in the circulation, in lymphoid organs secondary (SLO), in the intimal plaques and/or in the adventitial artery.

Under this paradigm, a work team that includes specialists from Ludwig Maximilians University in Munich, Germany, from the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, and Augusta University, in the United States, has carried out an investigation , recently published in Nature, confirmed that atherosclerosis is an autoimmune disease of T cells, and also began to reveal clues to the process.

T cells are involved in unresolvable inflammatory diseases as varied as cancers, infectious, chronic degenerative brain, autoimmune, and cardiovascular diseases. T cell immunity is tightly controlled at multiple tolerance testing points to prevent autoimmune injury.

“Our data support the possibility that peripheral T-cell tolerance in atherosclerosis may be disrupted at multiple key checkpoints in tissue- and T-cell subtype-specific ways,” explained Andreas JR Habenicht, one of the lead authors of the paper. document and specialist from Ludwig Maximilians University.

In addition, our findings provide a comprehensive view of the possible mechanisms of peripheral tolerance degradation in late-stage atherosclerosis and thus provide a robust blueprint for characterizing atherosclerosis as a T-cell-driven autoimmune disease that is associated with tolerance dysfunction.

As current data expand understanding of an underappreciated aspect of atherosclerosis, multiple targets for future therapeutic interventions may emerge, including restoration of tolerance checkpoints and T-cell therapy.

“Challenges for future work will involve experimentally intervening in mice and human clinical studies to determine which tolerance checkpoints affect the progression of atherosclerosis in ways similar to studies that have been done in various forms of human cancer,” Habenicht continued. .

In addition, new immune tolerance checkpoints not yet described by our findings may be discovered in the future.”

The scientists noted in their paper that impressions remain as to whether plaque-infiltrating T cells recognize disease-relevant atherosclerosis autoantigens. “It is one of the central unresolved questions in atherosclerosis,” Habenicht said.

Although our approach has not yet identified the relevant autoimmune hotspots, our data provide a tangible plan for the future to identify them, as we have defined three diverse T cell subsets with distinct roles in the atherosclerosis immune response.”