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Macrophage’s little helper: vitamin A directs alternatively activated monocyte-derived macrophages to tissue-resident macrophages

Cellular & Molecular Immunology volume 14, pages 805–808 (2017)Cite this article

Tissue-resident macrophages originate from the yolk sac in a Myb-independent manner and populate all organs during embryogenesis. These macrophages are a heterogeneous self-renewing population that adapt to the organ-specific local environment to contribute to tissue homeostasis. Depending on the age, organ and inflammatory conditions, macrophages that are derived from hematopoietic stem cells (HSCs) in a Myb-dependent manner may also infiltrate organs and develop into tissue-resident macrophages. The factors and mechanism driving the conversion of HSC-derived monocytes into tissue-resident macrophages are incompletely understood but may potentially offer the opportunity to therapeutically modulate tissue-specific inflammation. Recently, Gundra et al. presented the first evidence that activated monocytes recruited to the peritoneal cavity by a type 2 immune reaction can convert them into macrophages with the transcriptional profile of resident peritoneal macrophages.1 In addition, monocyte-derived macrophages can convert into tissue macrophages in Schistosoma mansoni-induced T helper cell type 2 (TH2)-dependent granuloma of the liver. Most notably, in the peritoneum and liver, the conversion of monocytes to tissue-resident macrophages lasts weeks and is vitamin A-dependent.

In contrast to tissue-resident macrophages, monocyte-derived macrophages express CXCR1, which allows genetic fate-mapping studies to differentiate between CXCR1+ monocyte-derived and CXCR1− tissue macrophages. Employing mice with the tamoxifen-inducible expression of Cre-recombinase under the control of the CXCR1 promotor and Cre-driven expression of a stable fluorescent marker (Cxcr1CreERT2-IRES-EYFP Rosastop-tdTomato reporter mice), Gundra et al. showed in situ that AAMmono converted into tissue-like resident macrophages and that AAMmono cells that persisted for eight weeks in the peritoneal cavity lost the capacity to re-express PD-L2 upon IL-4c stimulation. In addition, these converted cells (AAMconv) induced the expression of UCP1, which is also expressed in unstimulated AAMres.

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Authors and Affiliations

  1. Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, 39120, Germany

    Dirk Schlüter

  2. Organ-Specific Immune Regulation, Helmholtz-Center for Infection Research, Braunschweig 38124, Germany,

    Dirk Schlüter

  3. Innere Medizin II, Hämatologie und Onkologie, Universitätsklinikum Jena, Jena 07745, Germany,

    Florian H Heidel

  4. Leibniz-Institute on Aging, Fritz-Lipmann-Institute, Jena, Germany

    Florian H Heidel

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Correspondence to Dirk Schlüter.

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Schlüter, D., Heidel, F. Macrophage’s little helper: vitamin A directs alternatively activated monocyte-derived macrophages to tissue-resident macrophages. Cell Mol Immunol 14, 805–808 (2017). https://doi.org/10.1038/cmi.2017.58

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