The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Embryonic and Adult-Derived Resident Cardiac Macrophages Are Maintained through Distinct Mechanisms at Steady State and during Inflammation
Open accessAbstract
Cardiac macrophages are crucial for tissue repair after cardiac injury but are not well characterized. Here we identify four populations of cardiac macrophages. At steady state, resident macrophages were primarily maintained through local proliferation. However, after macrophage depletion or during cardiac inflammation, Ly6c(hi) monocytes contributed to all four macrophage populations, whereas resident macrophages also expanded numerically through proliferation. Genetic fate mapping revealed that yolk-sac and fetal monocyte progenitors gave rise to the majority of cardiac macrophages, and the heart was among a minority of organs in which substantial numbers of yolk-sac macrophages persisted in adulthood. CCR2 expression and dependence distinguished cardiac macrophages of adult monocyte versus embryonic origin. Transcriptional and functional data revealed that monocyte-derived macrophages coordinate cardiac inflammation, while playing redundant but lesser roles in antigen sampling and efferocytosis. These data highlight the presence of multiple cardiac macrophage subsets, with different functions, origins, and strategies to regulate compartment size.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“During the course of experimental autoimmune myocarditis (EAM), a significant increase in the number of pro-inflammatory Ly6Chi monocytes and recruited CCR2+ macrophages is observed throughout the cardiac tissue [7,8,10].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microglia in the developing brain proliferate locally at a low rate and are not normally replaced by other monocytes and macrophages from outside the brain, in contrast to most other tissue-resident macrophages (which also initially originate from yolk sac-derived macrophages, but are partially or fully replaced by fetal liver- or blood monocyte-derived macrophages [Bain et al., 2014, Calderon et”
From A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response (2017) · cites this paper as Epelman et al., 2014
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Clusters 1 and 5 had high expression of Ccr2, a marker of monocyte-derived macrophages that infiltrate from the circulation17-19 (Fig. 1J and Extended Data Fig. 1C-E).”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“Macrophages, which constitute a highly heterogeneous cell population, are key mediators in both maintaining homeostasis and the pathogenesis of myocardial injury [7,8].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“In the heart, two main lineages of macrophages with distinct origins and functions are distinguished: tissue-resident macrophages (TRMs; typically CCR2-), predominantly derived from embryonic development, and recruited monocyte-derived macrophages (CCR2+), which infiltrate from the bloodstream in response to injury [7,8,9,10].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Species-specific differences in macrophage ontogeny, cytokine networks, and the composition of the cardiac immune niche may limit direct extrapolation of findings [7].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Fate 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
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
Qian, B.-Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L. R., Kaiser, E. A., Snyder, L. A., & Pollard, J. W. (2011) · Nature · doi:10.1038/nature10138 · Cited by 2,874
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
Hashimoto, 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 · cited 3×
“transplanted monocytes, indicating local macrophage expansion in these niches despite genotoxic injury (Hashimoto et al., 2013).”
BackgroundResultInfluentialSelf-citationNahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J.-L., Libby, P., Weissleder, R., & Pittet, M. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070885 · Cited by 2,300
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
Self-citationSerbina, N. V., & Pamer, E. G. (2006) · Nature Immunology · doi:10.1038/ni1309 · Cited by 1,658
Jenkins, S. J., Rückerl, D., Cook, P. C., Jackson-Jones, L. H., Finkelman, F. D., van Rooijen, N., MacDonald, A. S., & Allen, J. E. (2011) · Science · doi:10.1126/science.1204351 · Cited by 1,404
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 1,342
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
Zigmond, 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 768
Self-citationSatpathy, A. T., Wumesh, K. C., Albring, J. C., Edelson, B. T., Kretzer, N. M., Bhattacharya, D., Murphy, T. L., & MURPHY, K. M. M. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120030 · Cited by 668
Self-citationMezzaroma, E., Toldo, S. A., Farkas, D., Seropian, I. M., Tassell, B. W. V., Salloum, F. N., Kannan, H. R., Menna, A. C., Voelkel, N. F., & Abbate, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108586108 · Cited by 642
Liver-resident NK cells confer adaptive immunity in skin-contact inflammation
Peng, H. C., Jiang, X., Chen, Y., Sojka, D. K., Wei, H., Gao, X., Sun, R., Yokoyama, W. M., & Tian, Z. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66381 · Cited by 558
Self-citationvan Amerongen, M. J., Harmsen, M. C., van Rooijen, N., Petersen, A. H., & van Luyn, M. J. A. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060547 · Cited by 544
Leuschner, F., Rauch, P. J., Ueno, T., Gorbatov, R., Marinelli, B. S., Lee, W. W., Dutta, P., Wei, Y., Robbins, C. S., Iwamoto, Y., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111009 · Cited by 536
Mounier, R., Théret, M., Arnold, L., Cuvellier, S., Bultot, L., Göransson, O., Sanz, N., Ferry, A., Sakamoto, K., Foretz, M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.06.017 · Cited by 464
Kumaravelu, P., Hook, L., Morrison, A. M., Ure, J. M., Zhao, S., Zuyev, S., Ansell, J., & Medvinsky, A. (2002) · Development · doi:10.1242/dev.129.21.4891 · Cited by 435
Tsujioka, H., Imanishi, T., Ikejima, H., Kuroi, A., Takarada, S., Tanimoto, T., Kitabata, H., Okochi, K., Arita, Y., Ishibashi, K., et al. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.021 · Cited by 387
Dendritic Cell and Macrophage Heterogeneity In Vivo
Hashimoto, D., Miller, J. C., & Mérad, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.007 · Cited by 378
Davies, L. C., Rosas, M., Jenkins, S. J., Liao, C., Scurr, M. J., Brombacher, F., Fraser, D. J., Allen, J. E., Jones, S. A., & Taylor, P. R. (2013) · Nature Communications · doi:10.1038/ncomms2877 · Cited by 349
Impaired Infarct Healing in Atherosclerotic Mice With Ly-6ChiMonocytosis
Panizzi, P. R., Świrski, F. K., Figueiredo, J., Waterman, P. R., Sosnovik, D. E., Aïkawa, E., Libby, P., Pittet, M. J., Weissleder, R., & Nahrendorf, M. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.08.089 · Cited by 326
Pinto, A. R., Paolicelli, R., Salimova, E., Gospocic, J., Slonimsky, E., Bilbao-Cortes, D., Godwin, J. W., & Rosenthal, N. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036814 · Cited by 318
Frangogiannis, N. G., Dewald, O., Xia, Y., Ren, G., Haudek, S. B., Leucker, T. M., Kraemer, D., Taffet, G. E., Rollins, B. J., & Entman, M. L. (2007) · Circulation · doi:10.1161/circulationaha.106.646091 · Cited by 289
Tacke, F., Ginhoux, F., Jakubzick, C., van Rooijen, N., Mérad, M., & Randolph, G. J. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052119 · Cited by 282
Self-citationBoyer, S. W., Schroeder, A. V., Smith‐Berdan, S., & Forsberg, E. C. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.04.021 · Cited by 245
Self-citationKaikita, K., Hayasaki, T., Okuma, T., Kuziel, W. A., Ogawa, H., & Takeya, M. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63309-3 · Cited by 214
Coordinate regulation of tissue macrophage and dendritic cell population dynamics by CSF-1
Tagliani, E., Shi, C., Nancy, P., Tay, C.-S., Pamer, E. G., & Erlebacher, A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110866 · Cited by 185
GM-CSF regulates intimal cell proliferation in nascent atherosclerotic lesions
Zhu, S.-N., Chen, M., Jongstra‐Bilen, J., & Cybulsky, M. I. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090866 · Cited by 166
Origins and functions of phagocytes in the embryo
Lichanska, A. M., & Hume, D. A. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(00)00157-0 · Cited by 155
Søndergaard, C. S., Hess, D. A., Maxwell, D. J., Weinheimer, C. J., Rosová, I., Creer, M. H., Piwnica-Worms, D. R., Kovács, A. D., Pedersen, L., & Nolta, J. A. (2010) · Journal of Translational Medicine · doi:10.1186/1479-5876-8-24 · Cited by 49
Listeriolysin O Is Strongly Immunogenic Independently of Its Cytotoxic Activity
Carrero, J. A., Vivanco-Cid, H., & Unanue, E. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032310 · Cited by 41
Self-citationNeurohormonal control of heart failure
Francis, G. S. (2011) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.78.s1.13 · Cited by 23
Flagged first, then by citations
Cited by
Sorted by citations
Macrophages in Tissue Repair, Regeneration, and Fibrosis
Wynn, T. A., & Vannella, K. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.015 · Cited by 4,481
Macrophages as regulators of tumour immunity and immunotherapy
DeNardo, D. G., & Ruffell, B. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0127-6 · Cited by 2,591
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
The Biological Basis for Cardiac Repair After Myocardial Infarction
Prabhu, S. D., & Frangogiannis, N. G. (2016) · Circulation Research · doi:10.1161/circresaha.116.303577 · Cited by 2,323
From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation
Italiani, P., & Boraschi, D. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00514 · Cited by 2,067
Metadata
- Authors
- 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., Schilling, J. D., Schwendener, R., Sergin, I., Razani, B., Forsberg, E. C., Yokoyama, W. M., Unanue, E. R., Colonna, M., Randolph, G. J., & Mann, D. L.
- Affiliations
- Washington University in St. Louis (US)
- University of California, Santa Cruz (US)
- University of Zurich (CH)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Mann, Douglas L.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 40
- Issue
- 1
- Pages
- 91-104
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3923301
- OpenAlex
- W2010484682
- Cited by
- 1,494
- References
- 34
- Citations by year
- 2026: 101 · 2025: 113 · 2024: 131 · 2023: 135 · 2022: 140 · 2021: 147 · 2020: 147 · 2019: 117 · 2018: 128 · 2017: 117 · 2016: 80 · 2015: 77 · 2014: 59
- FWCI
- 76.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- HAL (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- American Heart Association
- National Heart, Lung, and Blood Institute (K08HL112826, R01HL111094, T32HL007081)
- National Cancer Institute (T32CA009547)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100917)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- cardiac macrophages, tissue-resident macrophages, monocyte-derived macrophages, embryonic macrophages, yolk sac macrophages, monocyte proliferation, Ly6C+ monocytes, CCR2, cardiac inflammation, efferocytosis, antigen sampling, macrophage homeostasis
- MeSH terms
- Animals, Antigens, Ly, Cell Differentiation, Cells, Cultured, Heart, Homeostasis, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Myocarditis, Myocardium, Phagocytosis, Yolk Sac, Cell Death, Antigen Presentation, Cell Lineage, Myocytes, Cardiac, Fetal Development, Mice, Receptors, CCR2, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
