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Macrophages

Macrophage niche availability enables local monocyte proliferation in peripheral tissues

Nature Immunology volume 24, pages 743–745 (2023)Cite this article

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Mononuclear phagocyte proliferation is thought to be limited to myeloid progenitor cells and mature macrophages. However, availability within an interstitial macrophage niche permits the proliferation of monocytes in the lung before macrophage differentiation.

At least two transcriptionally distinct lung IM subsets have been identified that reside in different tissue niches and perform specific functions5,6. CD206+ (LYVE-1+MHCII−) IMs associate with blood vessels, proliferate locally, and secrete immuno-regulatory cytokines such as IL-10. CD206− (LYVE-1−MHCII+) IMs are located adjacent to nerve bundles and fibers, are less capable of self-renewal than CD206+ IMs, and exhibit antigen-presenting functions. IMs are probably of mixed origins, developing from the embryonic yolk sac and fetal liver before birth, and from bone marrow monocytes postnatally. In adulthood, IMs are long-lived and replenished by both self-renewal and differentiating monocytes. However, IM turnover is infrequent, making the study of replenishment dynamics especially challenging. To circumvent this issue, Vanneste et al.4 used CRISPR–Cas9-mediated engineering to generate Tmem119creCx3cr1LSL-DTR mice (referred to as IMDTR mice), in which cells expressing both Cx3cr1 and Tmem119 express the diphtheria toxin receptor (DTR) and are sensitive to diphtheria toxin-induced death. The addition of diphtheria toxin depletes both the CD206+ and CD206− lung IM subsets, while sparing alveolar macrophages. Combined with elegant congenic thorax-protected bone marrow transplant studies, the approach established that reconstituted IMs derive from bone marrow monocytes in a CCR2-dependent manner. This finding corroborates observations in other organs, including the liver, where monocytes can give rise to long-lived resident Kupffer cells if the niche is available7.

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Fig. 1: Repopulation of lung IMs depends in part on proliferation of blood monocytes, before they differentiate into mature macrophages.

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Authors and Affiliations

  1. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    Aniqa B. Khan & Clinton S. Robbins

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Clinton S. Robbins

  3. Peter Munk Cardiac Centre, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

    Clinton S. Robbins

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  1. Aniqa B. Khan
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  2. Clinton S. Robbins
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Correspondence to Clinton S. Robbins.

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Khan, A.B., Robbins, C.S. Macrophage niche availability enables local monocyte proliferation in peripheral tissues. Nat Immunol 24, 743–745 (2023). https://doi.org/10.1038/s41590-023-01482-5

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