Figure 1.

NK cells in atherosclerosis. From the site of atherosclerotic (ATS) plaque formation (A) many cytokines and chemokines are released into the blood, stimulating NK cells migration and entry within the plaque. Infiltrating NK cells can interact, by contact, with other immune cells such as (B) macrophages, that in presence of oxLDL, produce and release IL-12, thus potentiating cytolytic activity of NK via interferon γ (IFNγ) release. OxLDL can also be present as opsonized particles (C) that support dendritic cells (DCs)-NK crosstalk which is also mediated by CD48-2BA interaction and leads to (D) IFNγ release from NKs. IFNγ from NK cells exerts its effect on both (D) smooth muscle cells (SMCs) by inducing their apoptosis and macrophages by promoting M1-like phenotype switch. Furthermore, both (E) macrophages and endothelial cells (ECs) release soluble MICA (sMICA) that upon NKG2D binding on NK cells increase NK killing capability. Within ATS plaque, (F) a subset of NK cells display a hyperactive phenotype/behavior with increased expression of CD49a, CD56, CD69 and CD103 and NK cells (G) modify receptors expression downmodulated CD47 and increasing CD90 marker, leading to IFNγ release.