The role of immune cells in different stages of atherosclerosis

Atherosclerosis is often pictured as a plumbing problem — cholesterol clogging pipes. This review reframes it as what it actually is: an immune-driven disease, and maps the cast of immune cells at every stage.

Drawing on 170 references and modern single-cell sequencing, the authors catalog the players. On the innate side: monocytes, macrophages (far more varied than the old M1/M2 split implied), neutrophils and their plaque-destabilizing “NETs,” and dendritic cells. On the adaptive side, a tug-of-war — pro-inflammatory Th1 cells versus protective regulatory T cells, whose balance largely sets the pace of disease, with context-dependent contributions from other T and B cells. The recurring lesson is plasticity: immune cells shift phenotype with their environment.

The clinical relevance is that this is the rationale for anti-inflammatory cardiology. It explains why colchicine and IL-1β blockade (CANTOS) help, and why blanket immunosuppression backfires by inviting infection. The future it points to is precision immunomodulation — targeting specific cells or pathways rather than the whole system.

We rate the evidence solid: a comprehensive, current synthesis integrating cutting-edge single-cell data, balanced across pro- and anti-atherogenic mechanisms. Its clinical significance is moderate-to-high — it underpins an emerging class of therapies — but it rests largely on preclinical and observational work, with the human payoff still being worked out.