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NRI AT 20: MACROPHAGES

Tissue macrophages break dogma

Nature Reviews Immunology volume 21, page 625 (2021)Cite this article

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At the turn of the twenty-first century, macrophage biology appeared to be a mundane topic in research, as the field gave way to rapid growth in the study of dendritic cells. The blood monocyte was scarcely questioned as the de facto precursor for macrophages, but even the popularity of monocytes as a topic of research relied on their potential to differentiate into dendritic cells. Twenty years ago, entrenched dogma in the field was that proliferation of end-stage differentiated cells within the haematopoietic lineage was rare, so the concept that fully mature macrophages could proliferate while maintaining their differentiated status was akin to heresy. However, elegant work in 2009 by Aziz et al. upended that dogma by showing that macrophages were capable of self-renewal as fully differentiated cells. This proliferation occurred in the context of impaired expression of the transcription factor MafB, so the physiological context of when macrophage proliferation might occur in vivo was not entirely clear.

Nonetheless, these findings set the stage for the breaking of another dogma in the field — that of the widely accepted paradigm that adult bone marrow-derived monocytes were the precursors of all tissue macrophages. Employing a clever lineage tracing strategy, Ginhoux, Merad and colleagues (2010) revealed that primitive macrophages from the embryonic yolk sac gave rise to microglia, the macrophages of the brain. Indeed, these cells were sustained locally through self-proliferation so that even adult mice did not require monocytes for replenishment of this macrophage population.

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References

Original articles

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  1. Department of Pathology & Immunology, Washington University, St. Louis, MO, USA

    Gwendalyn J. Randolph

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  1. Gwendalyn J. Randolph
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Correspondence to Gwendalyn J. Randolph.

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Randolph, G.J. Tissue macrophages break dogma. Nat Rev Immunol 21, 625 (2021). https://doi.org/10.1038/s41577-021-00620-0

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