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

Uma Mahesh Gundra, Natasha M. Girgis, Dominik Ruckerl, Stephen Jenkins, Lauren N. Ward, Zachary D. Kurtz, Kirsten E. Wiens, Mei San Tang, Upal Basu-Roy, Alka Mansukhani, Judith E. Allen, P'ng Loke

Research output: Contribution to journalArticlepeer-review

278 Scopus citations

Abstract

Macrophages adopt an alternatively activated phenotype (AAMs) when activated by the interleukin-4receptor(R)α. AAMs can be derived either from proliferation of tissue resident macrophages or recruited inflammatory monocytes, but it is not known whether these different sources generate AAMs that are phenotypically and functionally distinct. By transcriptional profiling analysis, we show here that, although both monocyte and tissuederived AAMs expressed high levels of Arg1, Chi3l3, and Retnla, only monocyte-derived AAMs up-regulated Raldh2 and PD-L2. Monocyte-derived AAMs were also CX3CR1-green fluorescent protein (GFP)high and expressed CD206, whereas tissue-derived AAMs were CX3CR1-GFP and CD206 negative. Monocyte-derived AAMs had high levels of aldehyde dehydrogenase activity and promoted the differentiation of FoxP31 cells from naïve CD4+ cells via production of retinoic acid. In contrast, tissue-derived AAMs expressed high levels of uncoupling protein 1. 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.

Original languageEnglish
Pages (from-to)e110-e122
JournalBlood
Volume123
Issue number20
DOIs
StatePublished - May 15 2014

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