Defining the role(s) of selective subsets of antigen presenting cells in promoting or preventing atherosclerosis (renewal)

Atherosclerosis—the artery-clogging process behind most heart attacks and strokes—is driven in part by immune cells attacking low-density lipoproteins (LDL), but the specific cells that orchestrate this attack have remained unidentified. The problem is that while researchers know that certain T cells promote atherosclerosis and others protect against it, they do not know which antigen-presenting cells (APCs) are instructing those T cells. This gap has blocked efforts to develop immune-based treatments that could selectively dampen the harmful response without suppressing the entire immune system. The team recently discovered that one APC type—plasmacytoid dendritic cells—unexpectedly drives pro-atherogenic immunity, overturning previous assumptions. This project will use advanced genetic tools to systematically disable specific APC subsets in mice, revealing exactly which cells promote or prevent the disease. If successful, the work could identify new molecular targets for drugs that block the immune system’s contribution to atherosclerosis while leaving protective immunity intact. The research is fundamental science—it will not produce a treatment tomorrow—but understanding which cells orchestrate arterial inflammation is a prerequisite for designing therapies that stop it.