Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Nov 7:15:1475369.
doi: 10.3389/fimmu.2024.1475369. eCollection 2024.

Developmental programming of tissue-resident macrophages

Maria Francesca Viola #  1 , Eliana Franco Taveras #  1 , Elvira Mass  1
Affiliations
Review

Developmental programming of tissue-resident macrophages

Maria Francesca Viola et al. Front Immunol. .

Abstract

Macrophages are integral components of the innate immune system that colonize organs early in development and persist into adulthood through self-renewal. Their fate, whether they are replaced by monocytes or retain their embryonic origin, depends on tissue type and integrity. Macrophages are influenced by their environment, a phenomenon referred to as developmental programming. This influence extends beyond the local tissue microenvironment and includes soluble factors that can reach the macrophage niche. These factors include metabolites, antibodies, growth factors, and cytokines, which may originate from maternal diet, lifestyle, infections, or other developmental triggers and perturbations. These influences can alter macrophage transcriptional, epigenetic, and metabolic profiles, affecting cell-cell communication and tissue integrity. In addition to their crucial role in tissue immunity, macrophages play vital roles in tissue development and homeostasis. Consequently, developmental programming of these long-lived cells can modulate tissue physiology and pathology throughout life. In this review, we discuss the ontogeny of macrophages, the necessity of developmental programming by the niche for macrophage identity and function, and how developmental perturbations can affect the programming of macrophages and their subtissular niches, thereby influencing disease onset and progression in adulthood. Understanding these effects can inform targeted interventions or preventive strategies against diseases. Finally, understanding the consequences of developmental programming will shed light on how maternal health and disease may impact the well-being of future generations.

Keywords: developmental programming; hematopoiesis; macrophage; maternal immune activation (MIA); niche.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Factors determining macrophage functions. Macrophage function and longevity is a product of numerous, factors. Macrophages can derive from progenitors seeded within the embryo, or from differentiation of circulating monocytes. These cells are then further instructed by local cues and instructions from surrounding cells, the so-called macrophage ‘niche’. Finally, as discussed in more detail in this review, macrophages can be programmed by triggers during development, and retain this information throughout their lifespan. These factors are interconnected; for example, niche perturbations can impact monocyte recruitment, and developmental programming may also impact niche programming itself. Created using BioRender.
Figure 2
Figure 2
Developmental perturbations during hematopoiesis. The progenitors of tissue-resident macrophages develop in a series of waves during embryogenesis. As early as E8.5, erythro-myeloid progenitors (EMP) in the yolk sac give rise to pre-Macrophages (pMacs), which colonize the developing tissues and give rise to long-lived, proliferating tissue-resident macrophages. At E10.5, hematopoietic stem cells (HSCs) leave the aorta-gonado-mesonephros (AGM) region and migrate to the fetal liver. Here they expand, before migrating to the bone-marrow (BM) just before birth. In postnatal mice, bone-marrow derived monocytes can enter the tissue and differentiate into macrophages (MdM), possibly with different life cycles. The staggered timing of these developmental waves underlies the differential impact triggers can have. Acute triggers, depending on their timing, may program EMP/pMacs and/or HSCs, while chronic triggers may affect all lineages giving rise to macrophages. Created using BioRender.
See this image and copyright information in PMC

References

    1. Mass E, Nimmerjahn F, Kierdorf K, Schlitzer A. Tissue-specific macrophages: how they develop and choreograph tissue biology. Nat Rev Immunol. (2023) 9:563–79. doi: 10.1038/s41577-023-00848-y - DOI - PMC - PubMed
    1. Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, et al. . Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature. (2015) 518:547–51. doi: 10.1038/nature13989 - DOI - PMC - PubMed
    1. Mass E, Ballesteros I, Farlik M, Halbritter F, Günther P, Crozet L, et al. . Specification of tissue-resident macrophages during organogenesis. Science. (2016) 353. doi: 10.1126/science.aaf4238 - DOI - PMC - PubMed
    1. Yona S, Kim K-W, Wolf Y, Mildner A, Varol D, Breker M, et al. . Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis [Immunity 38 (2013) 79-91. Immunity. (2013) 38:79–91. doi: 10.1016/j.immuni.2013.05.008 - DOI - PMC - PubMed
    1. Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, et al. . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. (2013) 38:792–804. doi: 10.1016/j.immuni.2013.04.004 - DOI - PMC - PubMed

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work of this review was supported by the Jürgen Manchot PhD-Fellowship (to EFT), and the EMBO Postdoctoral fellowship 873-2023 (to MFV), by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy-EXC2151-390873048 (to EM), SFB 1454 - Project ID 432325352 – (to EM), FOR5547 – Project-ID 503306912 (to EM). EM is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 851257). This work was supported by the Open Access Publication Fund of the University of Bonn.

LinkOut - more resources