Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct

Macrophages adopt an alternatively activated phenotype (AAM) when activated by the IL-4Rα. AAM can be derived either from proliferation of tissue resident macrophages, or recruited inflammatory monocytes, but it is not known whether these different sources generate AAM that are phenotypically and functionally distinct. By transcriptional profiling analysis, we show here that while both monocyte and tissue-derived AAM expressed high levels of Arg1, Chi3l3 and Retnla, only monocyte-derived AAM upregulated Raldh2 and PD-L2. Monocyte-derived AAM were also CX3CR1-GFP(high) and expressed CD206, whereas tissue-derived AAM were CX3CR1-GFP and CD206 negative. Monocyte-derived AAM had high levels of aldehyde dehydrogenase (ALDH) activity and promoted the differentiation of FoxP3+ cells from naïve CD4(+) cells via production of retinoic acid. In contrast, tissue-derived AAM expressed high levels of UCP1. Hence monocyte-derived AAM have properties associated with immune regulation and the different physiological properties associated with AAM function may depend on the distinct lineage of these cells.