IL-10-producing macrophages preferentially clear early apoptotic cells

Efficient clearance of apoptotic cells seems to be a prerequisite to prevent the development of autoimmunity. Here we identify that macrophage colony-stimulating factor (M-CSF)-driven macrophages (M?2s) are potent phagocytes that have the unique capacity to preferentially bind and ingest early apoptotic cells. This macrophage subset has intrinsic anti-inflammatory properties, characterized by high interleukin-10 (IL-10) production in the absence of proinflammatory cytokines, such as IL-6 and tumor necrosis factor-alpha (TNF-alpha). Importantly, whereas the IL-6 and TNF-alpha production by granulocyte-macrophage (GM)-CSF-driven macrophages (M?1s) is inhibited upon uptake of apoptotic cells, the anti-inflammatory status of M?2 is retained during phagocytosis. M?2s were shown to use CD14 to tether apoptotic cells, whereas recognition of phosphatidylserine (PS) contributed to uptake of early apoptotic cells. M?2s showed more potent macropinocytosis compared with dendritic cells (DCs) and M?1s, and uptake of apoptotic cells was inhibited by a macropinocytosis inhibitor. Our studies suggest that, under steady-state conditions, IL-10-producing M?2s are prominently involved in the clearance of early apoptotic cells.