The transcriptome differences between IFN-I-elicited subsets of arginase 1-high and -low macrophages

Purpose: Using cells from the Arg1-YFP reporter mice, we discovered that only a part of macrophages from IFNβ-stimulated transitional monocytes showing Arg1-YFP expression. Therefore, we probed the overall differences between such IFN-I-elicited YFP+ and YFP- macrophages. Method: Bone marrow mononuclear cells from Arg1-YFP mice were treated with M-CSF± IFNβ for 64 h. The macrophages (F4/80+) in the control and IFN treatment group were further sorted by flow cytometry based on YFP intensities. The dominant YFP- population from the control cells (Con), as well as the YFP- (Treated1) and YFP+ (Treated2) subsets within IFNβ-treated cells were subjected to RNAseq analyses. Results: The most enriched biological functions for the up-regulated genes in the treated groups relate to immune activation, anti-viral responses and the IFN pathway. Most classical IFNβ downstream genes did not display differential expression between YFP- (Treated1) and YFP+ (Treated2). However, there are 84 genes displaying “Treated2 above Treated1” and 98 genes showing “Treated1 above Treated2” patterns. Conclusions: Our result show that IFN-I-elicited YFP+ and YFP- monocyte-derived macrophages tend to be M2- and M1-skewed, respectively. Con, Treated1 and Treated2 groups of samples were sorted by flow cytometry. Con and Threated1 each have three biological replicates, while Treated2 have two biological replicates.