Figure 1. Trafficking of circulating monocyte subsets.

Macrophage and dendritic cell precursors (MDPs) in the bone marrow give rise to LY6C^hi monocytes, which can serve as an intermediate for LY6C^low monocyte generation. LY6C^hi monocytes exit the bone marrow in a CC-chemokine receptor 2 (CCR2)-dependent manner and are recruited to inflamed tissues. Here, they can differentiate into TNF- and iNOS-producing dendritic cells (TIP DCs), inflammatory macrophages or inflammatory DCs, some of which can subsequently migrate to draining lymph nodes. LY6C^low monocytes patrol the blood vessel lumen by associating with the vascular endothelium. LY6C^low monocytes are also recruited to sites of inflammation and possibly contribute to wound healing by differentiating into alternatively activated macrophages. Under certain experimental conditions, LY6C^hi monocytes can give rise to Langerhans cells in the skin, microglia in the central nervous system, and CX₃C-chemokine receptor 1 (CX₃CR1)⁺ mononuclear phagocytes in the intestinal lamina propria, where they can sample the gut lumen by extending dendrites between intestinal epithelial cells. In the absence of inflammation, some circulating LY6C^hi monocytes return to the bone marrow. The spleen functions as a reservoir for monocytes outside the bone marrow. Following myocardial infarction, monocytes are released from splenic reservoirs, and LY6C^hi monocytes are selectively recruited to the injured heart.