Identity Crisis: CD301b(+) Mononuclear Phagocytes Blur the M1-M2 Macrophage Line

Mononuclear phagocytes (MNPs) are a highly heterogeneous group of cells that play important roles in maintaining the body’s homeostasis. Here, we found CD301b (also known as MGL2), a lectin commonly used as a marker for alternatively-activated macrophages (M2), was selectively expressed by a subset of CD11b+CD11c+MHCII+ MNPs in multiple organs including adipose tissues. Depleting CD301b+ MNPs in vivo led to a significant weight loss with increased insulin sensitivity and a marked reduction in serum RELM α, a multifunctional cytokine produced by MNPs. Reconstituting RELM α in CD301b+ MNP-depleted animals restored body weight and normoglycemia. Thus, CD301b+ MNPs play crucial roles in maintaining glucose metabolism and net energy balance.