Vitamin A mediates conversion of monocyte-derived macrophages into tissue resident macrophages during alternative activation

Abstract

It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80intCD206+PD-L2+MHCII+ macrophages into macrophages with a tissue-resident F4/80hiCD206−PD-L2−MHCII−UCP1+ phenotype in the peritoneal cavity of mice and during the formation of liver granulomas in mice infected with Schistosoma mansoni. The phenotypic conversion of F4/80intCD206+ macrophages into F4/80hiCD206− macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A–deficient mice infected with S. mansoni had disrupted liver granuloma architecture and increased mortality, which indicates that failure to convert macrophages from the F4/80intCD206+ phenotype to F4/80hiCD206− may lead to dysregulated inflammation during helminth infection.

DOI: 10.1038/ni.3734

Cite this paper

@inproceedings{Gundra2017VitaminAM, title={Vitamin A mediates conversion of monocyte-derived macrophages into tissue resident macrophages during alternative activation}, author={Uma Mahesh Gundra and Natasha M . Girgis and Michael A. Gonzalez and Mei San Tang and Hendrik J P Van Der Zande and Jian-Da Lin and Mireille Ouimet and Lily J Ma and Jordan Poles and Nikollaq Vozhilla and Edward A Fisher and Kathryn J . Moore and P. F. Loke}, booktitle={Nature Immunology}, year={2017} }