IL-27 induces a novel subset of M2 macrophages: characterization of IL-27-polarized macrophage using scRNA Seq 3792

Abstract Description M2 macrophages can be polarized into multiple subtypes (M2a, M2b, M2c, and M2d) by various stimuli. Previously, we reported that IL-27 polarizes M2 macrophages into HIV-resistant macrophages (27-Mac). Since IL-27 is a member of the IL-6 family of cytokines, and IL-6 polarizes M2 macrophages into M2d, we compared several cellular functions and gene expression profiles between 27-Mac and M2d in the current study. Monocytes derived from health donors were differentiated into M2 macrophages using M-CSF and then polarized into subtypes using IL-6, IL-27, or adenosine. Although IL-6 and IL-27 share gp130 to induce STAT3 signaling pathway, 27-Mac resisted HIV infection by more than 80% (p < 0.001). It enhanced the generation of reactive oxygen species (ROS) by greater than 3-fold (p < 0.001), whereas IL-6-polarized cells did not significantly affect either function. In contrast, adenosine analog (BAY60-6583)-polarized M2 macrophages (BAY-M2d) resisted HIV infection without affecting ROS production. The cytokine-producing profile of 27-Mac did not resemble those of the two subtypes. The expression profiles analysis using single-cell RNA sequencing with UMAP plots indicated that 27-Mac clustered differed from other cell types and significantly expressed CD38 by 6-fold (p < 0.01) and enhanced secretion of CXCL9 by more than 6,000-fold (p < 0.001) compared to M2. These data indicate that 27-Mac is distinct from traditional M2d. These results provide a new insight into the function of IL-27. Funding Sources NIAID/NIH: HHSH261200800001E Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)