Expansion of Regulatory T Cells Promotes the Clearance of Apoptotic Cells by Macrophages in Murine Atherosclerotic Plaques

A key process in inflammation resolution is efferocytosis, the clearance of apoptotic cells (AC) by phagocytes. Defective efferocytosis has been implicated in diseases characterized by chronic, nonresolving inflammation, including atherosclerosis. In atherosclerotic plaques, the accumulation of uncleared apoptotic cells leads to necrotic core formation, thereby increasing plaque instability, likelihood of rupture, and risk for acute cardiovascular events such as heart attack and stroke. Expansion of regulatory T cells (Tregs) in murine atherosclerosis decreases aortic root lesion area through mechanisms that are not fully understood. Given that Treg coordination of macrophage function has been reported, we hypothesized that expansion of the Treg compartment during advanced atherosclerosis promotes lesional efferocytosis. First, we used zymosan induced peritonitis as a proof-of-concept model to interrogate how Tregs may affect the efferocytic capacity of macrophages. Using mice in which the human diphtheri...