Common principles of macrophage biology in blood–tissue barriers
Abstract
Blood–tissue barriers play crucial roles in specialized tissues such as the central nervous system (CNS), eye, testis, and placenta. Tissue‐resident macrophages in these tissues are indispensable for maintaining tissue homeostasis and responding to pathological conditions. Recent advances in high‐throughput and high‐dimensional single‐cell analysis techniques, coupled with fate‐mapping tools, have revealed a remarkable diversity of tissue‐resident macrophages at the blood–tissue barrier. However, while comprehensive expression profiling has revealed the heterogeneity of macrophages within individual tissues, the commonalities of macrophages across anatomically similar structures like blood–tissue barriers remain poorly understood. This review focuses on the diversity and functional specialization of macrophages in tissues with blood–tissue barriers, highlighting recent insights into their anatomical distribution, developmental origins, phenotypic characteristics, and roles in maintaining tissue homeostasis. These findings may deepen our understanding of macrophage adaptation mechanisms in tissues with blood–tissue barriers, potentially leading to improved therapies for related disorders. Furthermore, examining the similarities and differences of macrophages across tissues may elucidate the molecular underpinnings of tissue‐specific adaptation mechanisms and functional specialization.
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Perivascular macrophages are located outside the parenchyma in the perivascular compartment surrounding arteries and veins as they penetrate into the brain parenchyma.
“They are located outside the parenchyma in the perivascular compartment surrounding arteries and veins, as they penetrate into the brain parenchyma (reviewed in [365].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [365]
Cites
Van Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Pombo Antunes, A. R., De Prijck, S., Vandamme, N., De Schepper, S., Van Isterdael, G., Scott, C. L., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0393-4 · Cited by 1,160 · cited 6× · see citing works
“15,34 Interest-ingly, unlike microglial precursor cells that settle in the parenchyma, precursor cells of CAMs establish themselves at the interfaces of the CNS.”
InfluentialChakarov, S., Lim, H. Y., Tan, L., Lim, S. Y., See, P., Lum, J., Zhang, X.-M., Foo, S., Nakamizo, S., Duan, K., et al. (2019) · Science · doi:10.1126/science.aau0964 · Cited by 1,114 · see citing works
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U.-K., Mack, M., Heikenwalder, M., Brück, W., Priller, J., & Prinz, M. (2007) · Nature Neuroscience · doi:10.1038/nn2015 · Cited by 1,089 · see citing works
Glia — more than just brain glue
Allen, N. J., & Barres, B. A. (2009) · Nature · doi:10.1038/457675a · Cited by 856 · see citing works
Ocular immune privilege: therapeutic opportunities from an experiment of nature
Streilein, J. W. (2003) · Nature Reviews Immunology · doi:10.1038/nri1224 · Cited by 807 · see citing works
Regulation of macrophage development and function in peripheral tissues
Lavin, Y., Mortha, A., Rahman, A., & Merad, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3920 · Cited by 680 · see citing works
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., & Pollard, J. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026317 · Cited by 649 · see citing works
Bonnardel, J., T’Jonck, W., Gaublomme, D., Browaeys, R., Scott, C. L., Martens, L., Vanneste, B., De Prijck, S., Nedospasov, S. A., Kremer, A., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.08.017 · Cited by 631 · see citing works
Greter, M., Lelios, I., Pelczar, P., Hoeffel, G., Price, J., Leboeuf, M., Kündig, T. M., Frei, K., Ginhoux, F., Merad, M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.11.001 · Cited by 630 · see citing works
Sakai, M., Troutman, T. D., Seidman, J. S., Ouyang, Z., Spann, N. J., Abe, Y., Ego, K. M., Bruni, C. M., Deng, Z., Schlachetzki, J. C. M., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.002 · Cited by 418 · see citing works
Macrophages at CNS interfaces: Ontogeny and function in health and disease
Kierdorf, K., Masuda, T., Jordão, M. J. C., & Prinz, M. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0201-x · Cited by 416 · cited 3× · see citing works
“5,14,18,26 These CAMs can be further subdivided into distinct subpopulations based on their specific anatomical locations within these interfaces.”
Self-citationA cellular and spatial map of the choroid plexus across brain ventricles and ages
Dani, N., Herbst, R. H., McCabe, C., Green, G. S., Kaiser, K., Head, J. P., Cui, J., Shipley, F. B., Jang, A., Dionne, D., et al. (2021) · Cell · doi:10.1016/j.cell.2021.04.003 · Cited by 388 · see citing works
FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data
Herman, J. S., Sagar, & Grün, D. (2018) · Nature Methods · doi:10.1038/nmeth.4662 · Cited by 363 · see citing works
Weller, R. O., Sharp, M. M., Christodoulides, M., Carare, R. O., & Møllgård, K. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1809-z · Cited by 222 · cited 2× · see citing works
“5,26,27 Perivascular macrophages (pvM Φ ) reside primarily within the perivascular space of arteries and arterioles, located between the vascular basement membrane and the astrocyte-derived parenchymal basement membrane, 6,15,30 while they are scarce along veins and absent in capillaries due to the…”
Mrdjen, D., Pavlovic, A., Hartmann, F. J., Schreiner, B., Utz, S. G., Leung, B. P., Lelios, I., Heppner, F. L., Kipnis, J., Merkler, D., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.02.014 · Cited by 220 · see citing works
A new genetic strategy for targeting microglia in development and disease
McKinsey, G. L., Lizama, C. O., Keown-Lang, A. E., Niu, A., Santander, N., Larpthaveesarp, A., Chee, E., Gonzalez, F. F., & Arnold, T. D. (2020) · eLife · doi:10.7554/elife.54590 · Cited by 176 · see citing works
Turnover of resident retinal microglia in the normal adult mouse
Xu, H., Chen, M., Mayer, E. J., Forrester, J. V., & Dick, A. D. (2007) · Glia · doi:10.1002/glia.20535 · Cited by 153 · see citing works
Mechanisms of myeloid cell entry to the healthy and diseased central nervous system
Amann, L., Masuda, T., & Prinz, M. (2023) · Nature Immunology · doi:10.1038/s41590-022-01415-8 · Cited by 50 · cited 15× · see citing works
“Brain Microglia Yolk sac-derived EMPs 14,15,33,35 Brain parenchyma 5,14,78 Hexb , 6,78 P2RY12*, 6,78,84 TMEM119* 6,78,85 Dural M Φ Yolk sac-derived EMPs with gradual replacement by HSC-derived cells 15,34 Dural sinuses and nonsinus space Perivascular M Φ Yolk sac-derived EMPs 6,14,15 Perivascular…”
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Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Bougnères, P., & Le Stunff, C. (2025) · Genes · doi:10.3390/genes16050590 · Cited by 11 · see citing works
- Authors
- Hiraga, S., & Masuda, T.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Hiraga, Shin‐ichiro
- Masuda, Takahiro
- Venue
- Clinical and Experimental Neuroimmunology
- Publisher
- Wiley
- Published
- 2024-09-23
- Volume
- 15
- Issue
- 4
- Pages
- 203-214
- ISSN
- 1759-1961 (ISSN-L)
- OpenAlex
- W4402725169
- Cited by
- 2
- References
- 18
- Citations by year
- 2025: 1 · 2024: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Experimental Neuroimmunology (publishedVersion)
- Kyushu University Institutional Repository (QIR) (Kyushu University) (acceptedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (23K21383)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- tissue-resident macrophages, blood-tissue barrier, macrophage heterogeneity, macrophage development, tissue homeostasis, central nervous system, placenta, testis, eye, single-cell analysis, fate mapping
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