Tissue-Resident Macrophage Ontogeny and Homeostasis
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Defining the origins and developmental pathways of tissue-resident macrophages should help refine our understanding of the role of these cells in various disease settings and enable the design of novel macrophage-targeted therapies. In recent years the long-held belief that macrophage populations in the adult are continuously replenished by monocytes from the bone marrow (BM) has been overturned with the advent of new techniques to dissect cellular ontogeny. The new paradigm suggests that several tissue-resident macrophage populations are seeded during waves of embryonic hematopoiesis and self-maintain independently of BM contribution during adulthood. However, the exact nature of the embryonic progenitors that give rise to adult tissue-resident macrophages is still debated, and the mechanisms enabling macrophage population maintenance in the adult are undefined. Here, we review the emergence of these concepts and discuss current controversies and future directions in macrophage biology.
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This is consistent with the current understanding that microglia derive from non-monocytic primitive myeloid precursors, unlike adult bone marrow-derived macrophages but similarly to some other tissue-resident macrophages.
“This is consistent with our current understanding of microglial development, which supports the notion that microglia derive from non-monocytic primitive myeloid cells acting as precursors, unlike adult bone marrow-derived macrophages, but similarly to some other tissue-resident macrophages 37.”
From Efficient derivation of microglia-like cells from human pluripotent stem cells (2016) · cites this paper as [37]
The PU.1-high, IRF8-high, MYB-low expression pattern in pMGLs is consistent with microglia emerging from PU.1- and IRF8-dependent but MYB-independent cells.
“consistent with microglia emerging from PU.1 and IRF8-dependent, but MYB-independent cells 34–37.”
From Efficient derivation of microglia-like cells from human pluripotent stem cells (2016) · cites this paper as [37]
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Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041 · see citing works
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175 · see citing works
Self-citationFate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245 · see citing works
Self-citationKanda, H. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26498 · Cited by 2,682 · see citing works
A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578 · see citing works
Hematopoiesis: An Evolving Paradigm for Stem Cell Biology
Orkin, S. H., & Zon, L. I. (2008) · Cell · doi:10.1016/j.cell.2008.01.025 · Cited by 2,570 · see citing works
Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., et al. (2015) · Nature · doi:10.1038/nature13989 · Cited by 2,339 · cited 6× · see citing works
“Given that, in adulthood, monocytes do not contribute to Kupffer cell (Gomez Perdiguero et al., 2015; Hoeffel et al., 2015; Schulz et al., 2012; Yona et al., 2013) or arterial macrophage (Ensan et al., 2016) populations, it appears that these tissues are somehow only temporarily ‘‘open’’ at birth but remain ‘‘closed’’…”
BackgroundMethodResultInfluentialHashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M. B., Leboeuf, M., Becker, C. D., See, P., Price, J., Lucas, D., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.004 · Cited by 2,311 · see citing works
Self-citationTranscriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation
Xue, J., Schmidt, S. V., Sander, J., Draffehn, A., Krebs, W., Quester, I., De Nardo, D., Gohel, T. D., Emde, M., Schmidleithner, L., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.006 · Cited by 2,210 · see citing works
Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment
Lavin, Y., Winter, D., Blecher-Gonen, R., David, E., Keren-Shaul, H., Merad, M., Jung, S., & Amit, I. (2014) · Cell · doi:10.1016/j.cell.2014.11.018 · Cited by 2,167 · see citing works
the Immunological Genome Consortium, Gautier, E. L., Shay, T., Miller, J., Greter, M., Jakubzick, C., Ivanov, S., Helft, J., Chow, A., Elpek, K. G., et al. (2012) · Nature Immunology · doi:10.1038/ni.2419 · Cited by 1,972 · cited 2× · see citing works
“Several studies have shown that macrophage populations exhibit distinct transcriptional signatures (Gautier et al., 2012; Lavin et al., 2014) and epigenetic marks (Gosselin et al., 2014; Lavin et al., 2014) that are specific to their tissue of residence.”
BackgroundMonocytes and macrophages: developmental pathways and tissue homeostasis
Ginhoux, F., & Jung, S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3671 · Cited by 1,840 · see citing works
Self-citationDendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny
Guilliams, M., Ginhoux, F., Jakubzick, C., Naik, S. H., Onai, N., Schraml, B. U., Segura, É., Tussiwand, R., & Yona, S. (2014) · Nature reviews. Immunology · doi:10.1038/nri3712 · Cited by 1,802 · see citing works
Self-citationMassively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types
Jaitin, D. A., Kenigsberg, E., Keren-Shaul, H., Elefant, N., Paul, F., Zaretsky, I., Mildner, A., Cohen, N., Jung, S., Tanay, A., et al. (2014) · Science · doi:10.1126/science.1247651 · Cited by 1,795 · see citing works
Local self-renewal can sustain CNS microglia maintenance and function throughout adult life
Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., & Rossi, F. M. V. (2007) · Nature Neuroscience · doi:10.1038/nn2014 · Cited by 1,643 · see citing works
THE ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES
van Furth, R., & Cohn, Z. A. (1968) · The Journal of Experimental Medicine · doi:10.1084/jem.128.3.415 · Cited by 1,564 · see citing works
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., Charo, I., Leibel, R. L., & Jr., A. W. F. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335 · Cited by 1,497 · see citing works
Epelman, S., Lavine, K. J., Beaudin, A. E., Sojka, D. K., Carrero, J. A., Calderon, B., Brija, T., Gautier, E. L., Ivanov, S., Satpathy, A. T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.11.019 · Cited by 1,494 · see citing works
Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways
Kierdorf, K., Erny, D., Goldmann, T., Sander, V., Schulz, C., Perdiguero, E. G., Wieghofer, P., Heinrich, A., Riemke, P., Hölscher, C., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3318 · Cited by 1,457 · see citing works
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335c1 · Cited by 1,424 · see citing works
Gosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.023 · Cited by 1,307 · see citing works
Guilliams, M., de Kleer, I., Henri, S., Post, S., Vanhoutte, L., Prijck, S. D., Deswarte, K., MALISSEN, B., Hammad, H., & Lambrecht, B. N. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20131199 · Cited by 1,259 · see citing works
Self-citationBain, C. C., Bravo-Blas, A., Scott, C. L., Gomez Perdiguero, E., Geissmann, F., Henri, S., Malissen, B., Osborne, L. C., Artis, D., & Mowat, A. M. (2014) · Nature Immunology · doi:10.1038/ni.2967 · Cited by 1,178 · see citing works
Hoeffel, G., Chen, J., Lavin, Y., Low, D., Almeida, F. F., See, P., Beaudin, A. E., Lum, J., Low, I., Forsberg, E. C., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.03.011 · Cited by 1,135 · see citing works
Self-citationvan Furth, R., Cohn, Z. A., Jg, H., Humphrey, J., Spector, W. G., & Langevoort, H. L. (1972) · PubMed Central · Cited by 1,133 · see citing works
Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors
Paul, F., Arkin, Y., Giladi, A., Jaitin, D. A., Kenigsberg, E., Keren-Shaul, H., Winter, D., Lara-Astiaso, D., Gury, M., Weiner, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.013 · Cited by 1,082 · see citing works
Self-citationInfiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool
Ajami, B., Bennett, J. L., Krieger, C., McNagny, K. M., & Rossi, F. M. V. (2011) · Nature Neuroscience · doi:10.1038/nn.2887 · Cited by 1,061 · see citing works
Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse
Palis, J., Robertson, S. M., Kennedy, M., Wall, C., & Keller, G. M. (1999) · Development · doi:10.1242/dev.126.22.5073 · Cited by 1,050 · see citing works
A Clonogenic Bone Marrow Progenitor Specific for Macrophages and Dendritic Cells
Fogg, D. K., Sibon, C., Miled, C., Jung, S., Aucouturier, P., Littman, D. R., Cumano, A., & Geissmann, F. (2005) · Science · doi:10.1126/science.1117729 · Cited by 1,050 · see citing works
A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis
Mucenski, M. L., McLain, K., Kier, A. B., Swerdlow, S. H., Schreiner, C. M., Miller, T. A., Pietryga, D. W., Scott, W. J., & Potter, S. S. (1991) · Cell · doi:10.1016/0092-8674(91)90099-k · Cited by 1,041 · see citing works
Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter
Chen, M. J., Yokomizo, T., Zeigler, B. M., Dzierzak, E. A., & Speck, N. A. (2009) · Nature · doi:10.1038/nature07619 · Cited by 1,016 · see citing works
Langerhans cells renew in the skin throughout life under steady-state conditions
Mérad, M., Manz, M. G., Karsunky, H., Wagers, A. J., Peters, W., Charo, I. F., Weissman, I. L., Cyster, J. G., & Engleman, E. G. (2002) · Nature Immunology · doi:10.1038/ni852 · Cited by 976 · see citing works
In Vivo Analysis of Dendritic Cell Development and Homeostasis
Liu, K., Victora, G. D., Schwickert, T. A., Guermonprez, P., Meredith, M. M., Yao, K.-H., Chu, F.-F., Randolph, G. J., Rudensky, A. Y., & Nussenzweig, M. C. (2009) · Science · doi:10.1126/science.1170540 · Cited by 953 · see citing works
Origin and differentiation of microglia
Ginhoux, F., Lim, S., Hoeffel, G., Low, D., & Huber, T. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00045 · Cited by 905 · cited 1× · see citing works
“In rodents, macrophages are present in the brain rudiment (for review, see Ginhoux et al., 2013) and developing skin (for review, see Ginhoux and Merad, 2010) as early as embryonic day (E)10.5.”
BackgroundInfluentialSelf-citationMicroglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain
Alliot, F., Godin, I., & Pessac, B. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00113-3 · Cited by 884 · see citing works
Okabe, Y., & Medzhitov, R. (2014) · Cell · doi:10.1016/j.cell.2014.04.016 · Cited by 884 · see citing works
Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells
Scott, C. L., Zheng, F., De Baetselier, P., Martens, L., Saeys, Y., De Prijck, S., Lippens, S., Abels, C., Schoonooghe, S., Raes, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms10321 · Cited by 860 · see citing works
Self-citationNew insights into the multidimensional concept of macrophage ontogeny, activation and function
Ginhoux, F., Schultze, J. L., Murray, P. J., Ochando, J., & Biswas, S. K. (2015) · Nature Immunology · doi:10.1038/ni.3324 · Cited by 832 · see citing works
Self-citationNaik, S. H., Sathe, P., Park, H., Metcalf, D., Proietto, A. I., Dakic, A., Carotta, S., O’Keeffe, M. A., Bahlo, M., Papenfuss, A. T., et al. (2007) · Nature Immunology · doi:10.1038/ni1522 · Cited by 817 · see citing works
Hoeffel, G., Wang, Y., Greter, M., See, P., Teo, P., Malleret, B., Leboeuf, M., Low, D., Oller, G., Almeida, F., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120340 · Cited by 786 · see citing works
Self-citationTamoutounour, S., Guilliams, M., Montanana Sanchis, F., Liu, H., Terhorst, D., Malosse, C., Pollet, E., Ardouin, L., Luche, H., Sanchez, C., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.004 · Cited by 783 · see citing works
Self-citationJakubzick, C. V., Gautier, E., Gibbings, S. L., Sojka, D. K., Schlitzer, A., Johnson, T. E., Ivanov, S., Duan, Q., Bala, S., Condon, T., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.007 · Cited by 762 · see citing works
Self-citationZigmond, E., Varol, C., Farache, J., Elmaliah, E., Satpathy, A. T., Friedlander, G., Mack, M., Shpigel, N. Y., Boneca, I. G., MURPHY, K. M. M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.08.026 · Cited by 754 · see citing works
The origin and development of nonlymphoid tissue CD103+ DCs
Ginhoux, F., Liu, K., Helft, J., Bogunovic, M., Greter, M., Hashimoto, D., Price, J. G., Yin, N., Bromberg, J. S., Lira, S. A., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20091756 · Cited by 744 · see citing works
Self-citationOnai, N., Obata-Onai, A., Schmid, M., Ohteki, T., Jarrossay, D., & Manz, M. G. (2007) · Nature Immunology · doi:10.1038/ni1518 · Cited by 699 · 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
Microglia Modulate Wiring of the Embryonic Forebrain
Squarzoni, P., Oller, G., Hoeffel, G., Pont‐Lezica, L., Rostaing, P., Low, D., Bessis, A., Ginhoux, F., & Garel, S. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.042 · Cited by 655 · see citing works
Self-citationOrigin of monocytes and macrophages in a committed progenitor
Hettinger, J., Richards, D. M., Hansson, J., Barra, M. M., Joschko, A.-C., Krijgsveld, J., & Feuerer, M. (2013) · Nature Immunology · doi:10.1038/ni.2638 · Cited by 643 · see citing works
Bruttger, J., Karram, K., Wörtge, S., Regen, T., Marini, F., Hoppmann, N., Klein, M., Blank, T., Yona, S., Wolf, Y., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.012 · Cited by 634 · see citing works
The development and maintenance of resident macrophages
Perdiguero, E. G., & Geissmann, F. (2015) · Nature Immunology · doi:10.1038/ni.3341 · Cited by 634 · see citing works
Tissue biology perspective on macrophages
Okabe, Y., & Medzhitov, R. M. (2015) · Nature Immunology · doi:10.1038/ni.3320 · Cited by 633 · see citing works
MYB function in normal and cancer cells
Ramsay, R. G., & Gonda, T. J. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2439 · Cited by 619 · see citing works
Local Proliferation of Macrophages Contributes to Obesity-Associated Adipose Tissue Inflammation
Amano, S. U., Cohen, J. L., Vangala, P., Tencerová, M., Nicoloro, S. M. C., Yawe, J. C., Shen, Y., Czech, M., & Aouadi, M. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.017 · Cited by 613 · see citing works
Schneider, C., Nobs, S. P., Kurrer, M. O., Rehrauer, H., Thiele, C., & Köpf, M. (2014) · Nature Immunology · doi:10.1038/ni.3005 · Cited by 603 · see citing works
van de Laar, L., Saelens, W., Prijck, S. D., Martens, L., Scott, C. L., Isterdael, G. V., Hoffmann, E., Beyaert, R., Saeys, Y., Lambrecht, B., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.017 · Cited by 576 · see citing works
Self-citationSchlitzer, A., Vijayakumar, S., Chen, J., Sumatoh, H., Schreuder, J., Lum, J., Malleret, B., Zhang, S., Larbi, A., Zolezzi, F., et al. (2015) · Nature Immunology · doi:10.1038/ni.3200 · Cited by 564 · see citing works
Self-citationZigmond, E., Bernshtein, B., Friedlander, G., Walker, C., Yona, S., Kim, K.-W., Brenner, O. J., Krauthgamer, R., Varol, C., Müller, W., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.03.012 · Cited by 560 · see citing works
Progressive replacement of embryo-derived cardiac macrophages with age
Molawi, K., Wolf, Y., Kandalla, P. K., Favret, J., Hagemeyer, N., Frenzel, K., Pinto, A. R., Klapproth, K., Henri, S., MALISSEN, B., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20140639 · Cited by 504 · see citing works
Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells
Sheng, J., Ruedl, C., & Karjalainen, K. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.016 · Cited by 482 · see citing works
Cell tracing shows the contribution of the yolk sac to adult haematopoiesis
Samokhvalov, I. M., Samokhvalova, N. I., & Nishikawa, S. (2007) · Nature · doi:10.1038/nature05725 · Cited by 461 · see citing works
Palis, J., & Yöder, M. C. (2001) · Experimental Hematology · doi:10.1016/s0301-472x(01)00669-5 · Cited by 445 · see citing works
McGrath, K. E., Frame, J. M., Fegan, K. H., Bowen, J. R., Conway, S. J., Catherman, S. C., Kingsley, P. D., Koniski, A. D., & Palis, J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.036 · Cited by 434 · see citing works
Ontogeny of the Hematopoietic System
Cumano, A., & Godin, I. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141538 · Cited by 432 · see citing works
Amit, I., Winter, D. R., & Jung, S. (2015) · Nature Immunology · doi:10.1038/ni.3325 · Cited by 406 · see citing works
Ensan, S., Li, A., Besla, R., Degousee, N., Cosme, J., Roufaiel, M., Shikatani, E. A., El-Maklizi, M., Williams, J. W., Robins, L., et al. (2016) · Nature Immunology · doi:10.1038/ni.3343 · Cited by 372 · see citing works
Ontogeny of Tissue-Resident Macrophages
Hoeffel, G., & Ginhoux, F. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00486 · Cited by 364 · see citing works
Self-citationTober, J. M., Koniski, A. D., McGrath, K. E., Vemishetti, R., Emerson, R. L., Bentley, K. L. D. M., Waugh, R. E., & Palis, J. (2006) · Blood · doi:10.1182/blood-2006-06-031898 · Cited by 328 · see citing works
Three pathways to mature macrophages in the early mouse yolk sac
Bertrand, J. Y., Jalil, A., Klaine, M., Jung, S., Cumano, A., & Godin, I. (2005) · Blood · doi:10.1182/blood-2005-02-0461 · Cited by 315 · see citing works
The pancreas anatomy conditions the origin and properties of resident macrophages
Calderon, B., Carrero, J. A., Ferris, S. T., Sojka, D. K., Moore, L., Epelman, S., Murphy, K. M., Yokoyama, W. M., Randolph, G. J., & Unanue, E. R. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20150496 · Cited by 308 · see citing works
Human dermal CD14(+) cells are a transient population of monocyte-derived macrophages
McGovern, N., Schlitzer, A., Gunawan, M., Jardine, L., Shin, A., Poyner, E., Green, K., Dickinson, R., Wang, X.-N., Low, D., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.08.006 · Cited by 281 · see citing works
Self-citationGibbings, S. L., Goyal, R., Desch, A. N., Leach, S. M., Prabagar, M. G., Atif, S. M., Bratton, D. L., Janssen, W. J., & Jakubzick, C. (2015) · Blood · doi:10.1182/blood-2015-01-624809 · Cited by 252 · see citing works
Local proliferation of macrophages in adipose tissue during obesity-induced inflammation
Haase, J., Weyer, U., Immig, K., Klöting, N., Blüher, M., Eilers, J., Bechmann, I., & Gericke, M. T. (2013) · Diabetologia · doi:10.1007/s00125-013-3139-y · Cited by 237 · see citing works
The hare and the tortoise: an embryonic haematopoietic race
Godin, I., & Cumano, A. (2002) · Nature reviews. Immunology · doi:10.1038/nri857 · Cited by 230 · see citing works
An Independent Subset of TLR Expressing CCR2-Dependent Macrophages Promotes Colonic Inflammation
Platt, A. M., Bain, C. C., Bordon, Y., Sester, D. P., & Mowat, A. M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903987 · Cited by 207 · see citing works
Microglial progenitors with a high proliferative potential in the embryonic and adult mouse brain.
Alliot, F., Lecain, É., Grima, B., & Pessac, B. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.4.1541 · Cited by 174 · see citing works
Development, differentiation, and phenotypic heterogeneity of murine tissue macrophages
Naito, M., Umeda, S., Yamamoto, T., Moriyama, H., Umezu, H., Hasegawa, G., Usuda, H., Shultz, L. D., & Takahashi, K. (1996) · Journal of Leukocyte Biology · doi:10.1002/jlb.59.2.133 · Cited by 169 · see citing works
Frame, J. M., McGrath, K. E., & Palis, J. (2013) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2013.09.006 · Cited by 155 · see citing works
From the Reticuloendothelial to Mononuclear Phagocyte System – The Unaccounted Years
Yona, S., & Gordon, S. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00328 · Cited by 150 · see citing works
THE KINETICS OF PROMONOCYTES AND MONOCYTES IN THE BONE MARROW
van Furth, R., & Dulk, M. M. C. D.-D. (1970) · The Journal of Experimental Medicine · doi:10.1084/jem.132.4.813 · Cited by 144 · see citing works
Engraftment of Embryonic Hematopoietic Cells in Conditioned Newborn Recipients
Yöder, M. C., & Hiatt, K. K. (1997) · Blood · doi:10.1182/blood.v89.6.2176 · Cited by 143 · see citing works
Price, J. G., Idoyaga, J., Salmon, H., Hogstad, B., Bigarella, C. L., Ghaffari, S., Leboeuf, M., & Mérad, M. (2015) · Nature Immunology · doi:10.1038/ni.3270 · Cited by 134 · see citing works
Ontogeny and homeostasis of Langerhans cells
Ginhoux, F., & Mérad, M. (2010) · Immunology and Cell Biology · doi:10.1038/icb.2010.38 · Cited by 133 · see citing works
Self-citationDevelopment, Differentiation, and Maturation of Macrophages in the Fetal Mouse Liver
Naito, M., Takahashi, K., & Nishikawa, S.-L. (1990) · Journal of Leukocyte Biology · doi:10.1002/jlb.48.1.27 · Cited by 115 · see citing works
Sumner, R., Crawford, A., Mucenski, M. L., & Frampton, J. (2000) · Oncogene · doi:10.1038/sj.onc.1203660 · Cited by 115 · see citing works
Sorokin, S. P., Hoyt, R. F., Blunt, D. G., & McNelly, N. A. F. (1992) · The Anatomical Record · doi:10.1002/ar.1092320410 · Cited by 114 · see citing works
Sathe, P., Metcalf, D., Vremec, D., Naik, S. H., Langdon, W. Y., Huntington, N. D., Wu, L., & Shortman, K. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.020 · Cited by 105 · see citing works
Mononuclear phagocytes of the intestine, the skin, and the lung
Scott, C. L., Henri, S., & Guilliams, M. (2014) · Immunological Reviews · doi:10.1111/imr.12220 · Cited by 104 · see citing works
Self-citationDistinct temporal requirements for Runx1 in hematopoietic progenitors and stem cells
Tober, J. M., Yzaguirre, A. D., Piwarzyk, E., & Speck, N. A. (2013) · Development · doi:10.1242/dev.094961 · Cited by 93 · see citing works
Clarke, D., Vegiopoulos, A., Crawford, A., Mucenski, M. L., Bonifer, C., & Frampton, J. (2000) · Oncogene · doi:10.1038/sj.onc.1203661 · Cited by 42 · see citing works
Mizoguchi, S., Takahashi, K., Takeya, M., Naito, M., & Morioka, T. (1992) · Journal of Leukocyte Biology · doi:10.1002/jlb.52.1.52 · Cited by 24 · see citing works
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Diversity, Mechanisms, and Significance of Macrophage Plasticity
Locati, M., Curtale, G., & Mantovani, A. (2020) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012718 · Cited by 2,199 · see citing works
Orecchioni, M., Ghosheh, Y., Pramod, A. B., & Ley, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01084 · Cited by 2,063 · see citing works
Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations
MacParland, S. A., Liu, J. C., Ma, X.-Z., Innes, B. T., Bartczak, A. M., Gage, B. K., Manuel, J., Khuu, N., Echeverri, J., Linares, I., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06318-7 · Cited by 1,552 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
Microglia Biology: One Century of Evolving Concepts
Prinz, M., Jung, S., & Priller, J. (2019) · Cell · doi:10.1016/j.cell.2019.08.053 · Cited by 1,525 · see citing works
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 · see citing works
Self-citationChakarov, 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
Self-citationThe Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis
Hirayama, D., Iida, T., & Nakase, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms19010092 · Cited by 927 · see citing works
Monocyte differentiation and antigen-presenting functions
Jakubzick, C. V., Randolph, G. J., & Henson, P. M. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.28 · Cited by 910 · see citing works
Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD
Na, Y. R., Stakenborg, M., Seok, S. H., & Matteoli, G. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0172-4 · Cited by 900 · see citing works
Phagocytosis: An Immunobiologic Process
Gordon, S. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.026 · Cited by 902 · see citing works
Self-Renewing Resident Cardiac Macrophages Limit Adverse Remodeling Following Myocardial Infarction
Dick, S. A., Macklin, J. A., Nejat, S., Momen, A., Clemente-Casares, X., Althagafi, M. G., Chen, J., Kantores, C., Hosseinzadeh, S., Aronoff, L., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0272-2 · Cited by 883 · see citing works
Self-citationCabeza-Cabrerizo, M., Cardoso, A., Minutti, C. M., Pereira da Costa, M., & Reis e Sousa, C. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053707 · Cited by 757 · see citing works
Bohlen, C. J., Bennett, F. C., Tucker, A. F., Collins, H. Y., Mulinyawe, S. B., & Barres, B. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.043 · Cited by 676 · see citing works
Efficient derivation of microglia-like cells from human pluripotent stem cells
Muffat, J., Li, Y., Yuan, B., Mitalipova, M., Omer, A., Corcoran, S., Bakiasi, G., Tsai, L.-H., Aubourg, P., Ransohoff, R. M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4189 · Cited by 651 · see citing works
Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation
Prinz, M., Masuda, T., Wheeler, M. A., & Quintana, F. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-110159 · Cited by 584 · see citing works
Abandoning M1/M2 for a Network Model of Macrophage Function
Nahrendorf, M., & Swirski, F. K. (2016) · Circulation Research · doi:10.1161/circresaha.116.309194 · Cited by 525 · see citing works
Establishment and Maintenance of the Macrophage Niche
Guilliams, M., Thierry, G. R., Bonnardel, J., & Bajenoff, M. (2020) · Immunity · doi:10.1016/j.immuni.2020.02.015 · Cited by 512 · see citing works
Self-citationGuidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531 · see citing works
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Blériot, C., Chakarov, S., & Ginhoux, F. (2020) · Immunity · doi:10.1016/j.immuni.2020.05.014 · Cited by 507 · see citing works
Self-citationSakai, 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
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Guilliams, M., & Scott, C. L. (2022) · Immunity · doi:10.1016/j.immuni.2022.08.002 · Cited by 395 · see citing works
Self-citationLund, H., Pieber, M., Parsa, R., Han, J., Grommisch, D., Ewing, E., Kular, L., Needhamsen, M., Espinosa, A., Nilsson, E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07295-7 · Cited by 249 · see citing works
Jain, N., Moeller, J., & Vogel, V. (2019) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-062117-121224 · Cited by 237 · see citing works
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Guilliams, M., & Svedberg, F. R. (2021) · Nature Immunology · doi:10.1038/s41590-020-00849-2 · Cited by 232 · see citing works
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Ben-Moshe, S., Veg, T., Manco, R., Dan, S., Papinutti, D., Lifshitz, A., Kolodziejczyk, A. A., Bahar Halpern, K., Elinav, E., & Itzkovitz, S. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.04.008 · Cited by 224 · see citing works
Liu, J., Liu, Z., Pang, Y., & Zhou, H. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01343-7 · Cited by 219 · see citing works
Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing
Li, C. M.-C., Shapiro, H., Tsiobikas, C., Selfors, L. M., Chen, H., Rosenbluth, J., Moore, K., Gupta, K. P., Gray, G. K., Oren, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108566 · Cited by 184 · see citing works
Contribution of adipose tissue to development of cancer
Cozzo, A. J., Fuller, A. M., & Makowski, L. (2017) · Comprehensive Physiology · doi:10.1002/cphy.c170008 · Cited by 188 · see citing works
Hepatic Stellate Cell-Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis
Matsuda, M., & Seki, E. (2020) · Seminars in Liver Disease · doi:10.1055/s-0040-1708876 · Cited by 189 · see citing works
“Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels
Nairz, M., Theurl, I., Swirski, F. K., & Weiss, G. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1944-8 · Cited by 178 · see citing works
A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages
Kim, J.-S., Kolesnikov, M., Peled-Hajaj, S., Scheyltjens, I., Xia, Y., Trzebanski, S., Haimon, Z., Shemer, A., Lubart, A., Van Hove, H., et al. (2021) · Immunity · doi:10.1016/j.immuni.2020.11.007 · Cited by 176 · see citing works
Zheng, X., Wang, X., Cheng, X., Liu, Z., Yin, Y., Li, X., Huang, Z., Wang, Z., Guo, W., Ginhoux, F., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00599-8 · Cited by 172 · see citing works
Self-citationMyeloid cell heterogeneity in cancer: not a single cell alike
Kiss, M., Van Gassen, S., Movahedi, K., Saeys, Y., & Laoui, D. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.02.008 · Cited by 159 · see citing works
Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes
Pallett, L. J., Burton, A. R., Amin, O. E., Rodriguez-Tajes, S., Patel, A. A., Zakeri, N., Jeffery-Smith, A., Swadling, L., Schmidt, N. M., Baiges, A., et al. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20200050 · Cited by 134 · see citing works
Human monocytes and macrophages regulate immune tolerance via integrin αvβ8–mediated TGFβ activation
Kelly, A., Gunaltay, S., McEntee, C. P., Shuttleworth, E. E., Smedley, C., Houston, S. A., Fenton, T. M., Levison, S., Mann, E. R., & Travis, M. A. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171491 · Cited by 124 · see citing works
Immunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126 · see citing works
Säwen, P., Eldeeb, M., Erlandsson, E., Kristiansen, T. A., Laterza, C., Kokaia, Z., Karlsson, G., Yuan, J., Soneji, S., Mandal, P. K., et al. (2018) · eLife · doi:10.7554/elife.41258 · Cited by 120 · see citing works
McMenamin, P. G., Saban, D. R., & Dando, S. J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.12.002 · Cited by 115 · see citing works
Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics
Liang, Y., Kaneko, K., Xin, B., Lee, J., Sun, X., Zhang, K., & Feng, G.-S. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.01.004 · Cited by 116 · see citing works
Bhlhe40 and Bhlhe41 Transcription Factors Regulate Alveolar Macrophage Self‐renewal and Identity
Rauschmeier, R., Gustafsson, C., Reinhardt, A., A‐Gonzalez, N., Tortola, L., Cansever, D., Subramanian, S., Taneja, R., Rossner, M. J., Sieweke, M. H., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018101233 · Cited by 102 · see citing works
Xiong, J., Xiao, R., Zhao, J., Zhao, Q., Luo, M., Li, F., Zhang, W., & Wu, M. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-023-04810-3 · Cited by 79 · see citing works
Role of macrophages in the endocrine system
Rehman, A., Pacher, P., & Haskó, G. (2021) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2020.12.001 · Cited by 71 · see citing works
STOP floxing around: Specificity and leakiness of inducible Cre/loxP systems
Stifter, S. A., & Greter, M. (2020) · European Journal of Immunology · doi:10.1002/eji.202048546 · Cited by 48 · see citing works
Lopez‐Atalaya, J. P., Askew, K. E., Sierra, A., & Gomez‐Nicola, D. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22545 · Cited by 49 · see citing works
Overlapping evidence of innate immune dysfunction in psychotic and affective disorders
Hughes, H. K., & Ashwood, P. (2020) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2020.100038 · Cited by 39 · see citing works
Iwata, A., Maruyama, J., Natsuki, S., Nishiyama, A., Tamura, T., Tanaka, M., Shichino, S., Seki, T., Komai, T., Okamura, T., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06357-5 · Cited by 25 · see citing works
“Once monocytes arrive at their tissue of destination, they undergo extensive differentiation depending on the environmental cues provided by tissue-speci fi c niches, enabling their development into specialized macrophages that support local tissue function 38,39 .”
A novel strategy to dissect multifaceted macrophage function in human diseases
Karlinsey, K., Qu, L., Matz, A. J., & Zhou, B. (2022) · Journal of Leukocyte Biology · doi:10.1002/jlb.6mr0522-685r · Cited by 23 · see citing works
Li, C., Ma, Z., Wei, X., Wang, Y., Wu, J., Li, X., Sun, X., Ding, Z., Yang, C., & Zou, Y. (2025) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-024-10577-9 · Cited by 13 · see citing works
Targeting macrophages in liver fibrosis
González del Barrio, L., Ipsen, D. H., Pfister, D. R., Hancz, D., & Scott, C. L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1835489 · Cited by 3 · see citing works
“For more details, we refer you to the extensive reviews on this topic (19, 20).”
- Authors
- Ginhoux, F., & Guilliams, M.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Ghent University (BE)
- Corresponding author
- Ginhoux, Florent
- Guilliams, Martin
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 44
- Issue
- 3
- Pages
- 439-449
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2301038687
- Cited by
- 1,884
- References
- 90
- Citations by year
- 2026: 183 · 2025: 177 · 2024: 210 · 2023: 180 · 2022: 233 · 2021: 224 · 2020: 211 · 2019: 180 · 2018: 133 · 2017: 99 · 2016: 39 · 2015: 1 · 2014: 1 · 2012: 1
- FWCI
- 14.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- tissue-resident macrophages, macrophage ontogeny, macrophage homeostasis, embryonic hematopoiesis, monocyte-derived macrophages, bone marrow, macrophage self-renewal, macrophage-targeted therapy
- MeSH terms
- Adult, Animals, Bone Marrow, Cell Differentiation, Hematopoiesis, Homeostasis, Humans, Inflammation, Macrophages, Embryonic Development
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