Abstract Body: Atherosclerosis is a chronic inflammatory disease, yet the mechanisms governing immune cell behavior changes between progressing and regressing plaques remains unexplored. To define how immune networks are remodeled as plaque inflammation resolves, we integrated spatial and global mouse transcriptomic and proteomic datasets in a model-agnostic framework. Deep phenotyping uncovered a novel Trem2⁺ macrophage population distinguished by expression of the intermediate filament protein Nestin that was selectively enriched during atherosclerosis regression. Using an in vivo proximity-labeling system to track ligand-receptor interactions, we found that Nestin⁺ macrophages (NesMφ) directly and preferentially engaged regulatory T cells (T_reg) in regressing lesions. This interaction was mediated by insulin-like growth factor 1 (IGF-1) signaling through its receptor, IGF-1R. Pharmacologic blockade of IGF-1R impaired efferocytosis and sustained necrosis within plaques, undoing regression. Our findings identify NesMφ as key effectors of inflammation resolution and highlight macrophage-T_reg communication through IGF-1 signaling as a central pathway enabling active atherosclerosis regression.