CD301b⁺ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha

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, 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 Resistin-like molecule (RELM) α, a multifunctional cytokine produced by MNPs. Reconstituting RELMα in CD301b⁺ MNP-depleted animals restored body weight and normoglycemia. Thus, CD301b⁺ MNPs play crucial roles in maintaining glucose metabolism and net energy balance.