A novel study identifies distinct molecular markers for classically activated M1 and alternatively activated M2 macrophages in mice. The research team performed a comprehensive analysis of the transcriptional signatures of murine M0, M1, and M2 macrophages, identifying genes that are uniquely or commonly expressed in each subset. They validated that CD38, G-protein coupled receptor 18 (Gpr18), and Formyl peptide receptor 2 (Fpr2) are specifically expressed in M1 macrophages, while Early growth response protein 2 (Egr2) and c-Myc are uniquely expressed in M2 macrophages. These markers were further confirmed using flow cytometry, showing that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages than the canonical M2 marker Arginase-1, while CD38 labeled most in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. The study provides novel and improved tools to distinguish M1 and M2 murine macrophages, defining exclusive and common signatures for these subsets. The findings suggest that CD38 and Egr2 are robust markers for M1 and M2 macrophages, respectively, and could improve the detection and understanding of macrophage phenotypes in both in vivo and in vitro settings. The study also highlights the importance of these markers in macrophage function and disease processes, offering potential therapeutic targets for macrophage modulation.A novel study identifies distinct molecular markers for classically activated M1 and alternatively activated M2 macrophages in mice. The research team performed a comprehensive analysis of the transcriptional signatures of murine M0, M1, and M2 macrophages, identifying genes that are uniquely or commonly expressed in each subset. They validated that CD38, G-protein coupled receptor 18 (Gpr18), and Formyl peptide receptor 2 (Fpr2) are specifically expressed in M1 macrophages, while Early growth response protein 2 (Egr2) and c-Myc are uniquely expressed in M2 macrophages. These markers were further confirmed using flow cytometry, showing that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages than the canonical M2 marker Arginase-1, while CD38 labeled most in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. The study provides novel and improved tools to distinguish M1 and M2 murine macrophages, defining exclusive and common signatures for these subsets. The findings suggest that CD38 and Egr2 are robust markers for M1 and M2 macrophages, respectively, and could improve the detection and understanding of macrophage phenotypes in both in vivo and in vitro settings. The study also highlights the importance of these markers in macrophage function and disease processes, offering potential therapeutic targets for macrophage modulation.