Monocyte phenotypes: When local education counts

432 INSIGHTS | The Journal of Experimental Medicine Monocytes are a heterogeneous population of phagocytic cells that are generated in the bone marrow and released into the bloodstream. There are two main monocyte subsets in mice: “inflammatory” monocytes that are Ly6C CCR2 CX 3 CR1 and “alternative” or “patrolling” monocytes that are Ly6C CCR2 CX 3 CR1. The process of monocyte recruitment and differentiation is still a matter of controversy. In this issue, Dal-Secco et al. report in situ monocyte reprogramming in the liver, from proinflammatory CCR2 CX 3 CR1 cells into reparative CCR2 CX 3 CR1 cells and show, for the first time, that this occurs at the site of injury. Dal-Secco et al. harnessed the power of imaging technology and fluorescent reporter mice to track monocytes in a model of sterile inflammation in the liver (induced after a 30 μm burn by a thermal probe). In this model, the recruitment of monocytes is dependent on CCR2 present on CCR2 CX 3 CR1 monocytes. Some of these cells were observed patrolling the liver sinusoids in the steady state. Within 24–48 hours, CCR2 CX 3 CR1 monocytes extravasated and formed a ring structure surrounding the necrotic tissue at the site of the injury. These extravascular monocytes started to differentiate and, by 48–72 hours, had lost CCR2 expression and gained CX 3 CR1 and MHC class II expression (CCR2 CX 3 CR1 CD11b MHCII CD64 F4/80). Blocking IL-10 and IL-4 delayed this phenotypic transition and impaired wound healing as shown by failure to clear necrotic hepatocytes and failure to deposit collagen.