Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct.
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 tissue-derived 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 FoxP3(+) 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.
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Uma Mahesh
UM
Gundra
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Natasha M
NM
Girgis
Centre for Immunity, Infection and Evolution, and the Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Dominik
D
Ruckerl
Centre for Immunity, Infection and Evolution, and the Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Stephen
S
Jenkins
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Lauren N
LN
Ward
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Zachary D
ZD
Kurtz
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Kirsten E
KE
Wiens
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Mei San
MS
Tang
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Upal
U
Basu-Roy
Department of Microbiology, New York University School of Medicine, New York, NY; and.
Alka
A
Mansukhani
Centre for Immunity, Infection and Evolution, and the Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Judith E
http://orcid.org/0000-0002-3829-066X
JE
Allen
Department of Microbiology, New York University School of Medicine, New York, NY; and.
P'ng
P
Loke
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000032:analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D007473:Ion Channels / Q000032:analysis / Q000235:genetics; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000032:analysis / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000071256:Uncoupling Protein 1
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1