Macrophage heterogeneity and efferocytosis: Beyond the M1/M2 dichotomy

Macrophage activation and polarization: nomenclature and experimental guidelines

Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.008 · Cited by 6,337 · see citing works

M-1/M-2 Macrophages and the Th1/Th2 Paradigm

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Single-cell immune landscape of human atherosclerotic plaques

Fernandez, D. M., Rahman, A. H., Fernandez, N. F., Chudnovskiy, A., Amir, E.-A. D., Amadori, L., Khan, N. S., Wong, C. K., Shamailova, R., Hill, C. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0590-4 · Cited by 970 · see citing works

CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis

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Macrophages in Atherosclerosis Regression

Barrett, T. J. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312802 · Cited by 633 · see citing works

Efferocytosis induces macrophage proliferation to help resolve tissue injury

Gerlach, B. D., Ampomah, P. B., Yurdagul, A., Liu, C., Lauring, M. C., Wang, X., Kasikara, C., Kong, N., Shi, J., Tao, W., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.10.015 · Cited by 360 · see citing works

STAT6 induces expression of Gas6 in macrophages to clear apoptotic neutrophils and resolve inflammation

Nepal, S., Tiruppathì, C., Tsukasaki, Y., Farahany, J., Mittal, M., Rehman, J., Prockop, D. J., & Malik, A. B. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821601116 · Cited by 136 · see citing works

CD147 Sparks Atherosclerosis by Driving M1 Phenotype and Impairing Efferocytosis

Lv, J., Wang, H., Zhang, C., Zhang, T.-J., Wei, H.-L., Liu, Z., Ma, Y.-H., Yang, Z. P., He, Q., Wang, L.-J., et al. (2024) · Circulation Research · doi:10.1161/circresaha.123.323223 · Cited by 98 · see citing works

Atherosclerosis is a major human killer and non-resolving inflammation is a prime suspect

Fredman, G., & MacNamara, K. C. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab309 · Cited by 52 · see citing works

Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients

Idrus, F. N. M., Ahmad, N. S., Hoe, C. H., Azlan, M., Norfuad, F. A., Yusof, Z., Isa, W. Y. H. W., Ali, A. A. M., & Yvonne-Τee, G. B. (2021) · BMC Immunology · doi:10.1186/s12865-021-00410-2 · Cited by 31 · see citing works

Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug–Gene Networks: From Biology to Precision Therapeutics

Decano, J. L., Maiorino, E., Matamalas, J. T., Chelvanambi, S., Tiemeijer, B. M., Yanagihara, Y., Mukai, S., Jha, P. K., Pestana, D. V. S., D'Souza, E. D. A., et al. (2023) · Circulation · doi:10.1161/circulationaha.123.064794 · Cited by 29 · see citing works

Macrophage Heterogeneity Complicates Reversal of Calcification in Cardiovascular Tissues

Rogers, M. A., Aikawa, M., & Aïkawa, E. (2017) · Circulation Research · doi:10.1161/circresaha.117.311219 · Cited by 28 · see citing works

Dynamic Macrophages: Understanding Mechanisms of Activation as Guide to Therapy for Atherosclerotic Vascular Disease

Decano, J. L., & Aikawa, M. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00097 · Cited by 28 · see citing works

Circulating Gas6 is associated with reduced human carotid atherosclerotic plaque burden in high risk cardiac patients

Holden, R. M., Hétu, M., Li, T. Y., Ward, E., Couture, L., Herr, J. E., Christilaw, E., Adams, M. A., & Johri, A. M. (2018) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2018.11.018 · Cited by 14 · see citing works

Macrophage polarization in sepsis: Emerging role and clinical application prospect

Hou, F., Mi, J. H., Wang, Q., Tao, Y. L., bin Guo, S., Ran, G. H., & Wang, J. C. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113715 · Cited by 36 · see citing works

Vascular inflammation in chronic kidney disease: the role of uremic toxins in macrophage activation

Jha, P. K., Nakano, T., Itto, L. Y. U., Barbeiro, M. C., Lupieri, A., Aikawa, E. R., & Aikawa, M. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1574489 · Cited by 29 · see citing works

Mitochondrial dynamics and metabolism in macrophages for cardiovascular disease: A review

Zhong, Y.-L., Xu, C.-Q., Li, J., Liang, Z., Wang, M., Ma, C., Jia, C., Cao, Y., & Chen, J. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156620 · Cited by 25 · see citing works

Metrnl ameliorates myocardial ischemia–reperfusion injury by activating AMPK-mediated M2 macrophage polarization

Chen, D., Feng, Y.-Y., Wang, H., Lu, C., Liu, D.-Z., Chen, G., Xue, Y., Na, N., & Huang, F. (2025) · Molecular Medicine · doi:10.1186/s10020-025-01150-4 · Cited by 25 · see citing works

Rebalancing immune homeostasis in combating disease: The impact of medicine food homology plants and gut microbiome

Xia, L., Li, C., Zhao, J., Sun, Q., & Mao, X. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156150 · Cited by 22 · see citing works

Precision cardiovascular medicine: shifting the innovation paradigm

Aikawa, M., Sonawane, A. R., Chelvanambi, S., Asano, T., Halu, A., Matamalas, J. T., Singh, S. A., Uchida, S., Aïkawa, E., Arenas, À., et al. (2025) · Frontiers in Science · doi:10.3389/fsci.2025.1474469 · Cited by 22 · see citing works

Macrophage-induced immunomodulation in oral tissue repair and regeneration: Recent advances and future perspectives

Wang, Y., Mao, J., Wang, Y., Wang, R., Duan, D., Liu, Z., Hu, X., Yu, Z., & Shi, X. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.11.057 · Cited by 20 · see citing works

Efferocytosis and Bone Dynamics

Batoon, L., Hawse, J. R., McCauley, L. K., Weivoda, M. M., & Roca, H. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-024-00878-y · Cited by 15 · see citing works

Macrophages: emerging targets for ulcerative colitis

Chen, S., Qin, Z., Lin, X., Zhou, S., Xu, Y., & Zhu, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1623491 · Cited by 13 · see citing works

Role of macrophages in vascular calcification: From the perspective of homeostasis

Dong, R., Ji, Z., Wang, M., & Ma, G. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113635 · Cited by 11 · see citing works

Epithelial redox stress programs macrophage immunometabolism through a ZNF24-MIF–NF–κB pathway in chronic nonbacterial prostatitis

Zhang, F., Zhang, A., Meng, T., Liu, X., Yang, C., Liang, C., & Zhang, M. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104042 · Cited by 9 · see citing works

MicroRNA-26b−/− augments atherosclerosis, while mimic-loaded nanoparticles reduce atherogenesis

Peters, L. J. F., Bidzhekov, K., Bonnin-Marquez, A., Sundararaman, S. S., Huchzermeier, R., Maas, S. L., Abschlag, K., Jans, A., Lin, C., Haberbosch, M., et al. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf234 · Cited by 8 · see citing works

Exploitable mechanisms of antibody and CAR mediated macrophage cytotoxicity

Liu, T., Zhang, M., Farsh, T., Li, H., Kishishita, A., Barpanda, A., Leung, S. G., Zhu, J., Jung, H., Hua, J. T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60745-x · Cited by 6 · see citing works

Biomaterial-based strategies for cell-free nucleic acids scavenging and macrophage modulation in oral diseases: Mechanisms and therapeutic potential

Chen, J., Xu, C., Zhang, S., Sui, H., Fang, K., Li, S. L., Yang, R., Yang, C., Shao, D., Zheng, Q., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123773 · Cited by 6 · see citing works

Nrf2 deficiency in myeloid cells accelerates atherosclerosis by promoting the inflammatory response and impairing efferocytosis

Xu, X., Liu, C., Bo, J., Wang, H., Zhang, Y., Xu, Y., Fu, J., Pi, J., & Wang, H. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.01.005 · Cited by 5 · see citing works

Macrophage efferocytosis: Mechanisms and therapeutic opportunities for future cardiovascular diseases

Su, Y., Wang, H., Liu, H., & Tang, Y. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115899 · Cited by 4 · see citing works

OnabotulinumtoxinA alters pro- and anti-inflammatory dural macrophage response to CSD in female mice

Schain, A. J., Fajardo, D. D., Strassman, A. M., Kulkarni, S., Broide, R. S., Brideau-Andersen, A. D., Adams, A. M., Brin, M. F., & Burstein, R. (2025) · Cephalalgia · doi:10.1177/03331024251378730 · Cited by 4 · see citing works

Aβ impairs bone vascular homeostasis in APP/PS1 mice via disrupting the mitochondrial fission-efferocytosis axis in macrophages

Liu, T., Zhang, W., Bao, W., Wang, X., Zhang, F., Guo, J., & Li, M. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115526 · Cited by 3 · see citing works

Naja atra SVPLA2 Aggravates Acute Kidney Injury Through Metabolic Reprogramming-Dependent Macrophage Polarization and Defective Efferocytosis

Liu, J., Wen, Z., Tang, S., Wu, J., Bi, X., Yang, Y., & Huang, C. (2026) · Toxins · doi:10.3390/toxins18040155 · Cited by 3 · see citing works

Polysaccharide-engineered mitochondria reprogram macrophages to resolve diabetic wound inflammation and promote repair

Yu, C., Feng, Q., Liao, Y., Tan, M., Zhao, Y., Chen, L., Zhang, W., Lin, C., Zeng, R., Al-Smadi, F., et al. (2026) · Bioactive Materials · doi:10.1016/j.bioactmat.2026.04.009 · Cited by 3 · see citing works

Immunological characteristics and functions of macrophages in Mycobacterium leprae infection

Zhang, X., Jiang, H., Liu, W., & Wang, H. (2025) · BMC Immunology · doi:10.1186/s12865-025-00759-8 · Cited by 2 · see citing works

Thrombospondin-1-mediated macrophage efferocytosis dysfunction exacerbates intestinal pathology in Hirschsprung's disease

Li, Q., Kong, H., Li, Q., Chen, T., Chen, L., Wang, F., Zhang, X., Wu, Y., Zhu, Y., Geng, Z., et al. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116344 · Cited by 2 · see citing works

Sequential Macrophage Polarization Mediated by a Biphasic Cold Plasma Pen for Oral Ulcer Therapy

Gong, X., Yu, D., Yang, H., Wang, H., Bai, Y., Zheng, Z., & Chen, W. (2026) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5c25563 · Cited by 2 · see citing works

Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics

Chen, L., Chen, Y., Zhao, M., Yang, X., Sutte, K., Lu, M., Chen, J., Zheng, X., Yang, D., & Liu, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1814879 · Cited by 1 · see citing works

Single-cell RNA sequencing identifies a unique ZEB2-Regulated Clec4d+ macrophage state contributing to early inflammatory injury in cardiac hypertrophy

Zhang, M., Zhang, B., Tao, Q.-Q., Wang, X.-Y., Guan, X.-X., Dong, Z., Guo, X., Qi, W., Cheng, W.-Z., Zhang, X., et al. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177867 · Cited by 1 · see citing works

Unraveling the mechanism of tripterygium glycosides tablets-induced liver injury and the protective role of total glucosides of peony from immune-metabolic dysregulation to multi-cellular cascade

Zhang, Y., Ding, Z., Wang, X., Shen, J., Chen, L., Chen, L., Chen, W., Zhang, Y., & Zhang, Y. (2026) · Chinese Medicine · doi:10.1186/s13020-026-01373-5 · Cited by 1 · see citing works

Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies

Lei, Y., Tang, M., Deng, H., Li, Y., Wu, J., Luo, L., Mou, Y., 吴千石, Li, Q., Xu, Y., et al. (2026) · Inflammation Research · doi:10.1007/s00011-026-02302-w · Cited by 1 · see citing works

PDE3A2 modRNA Fine-Tunes Nuclear cAMP Microdomains and Reverses Pathological Cardiac HypertrophyPreprint

Xiang, W., Lian, M., Guan, Q., Sun, X., Li, S., Lu, H., Qin, G., Xiang, Y. K., Ni, H., & Wang, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.30.679675

Immunotherapy with Pro-regenerative Macrophages from Embryonic Stem Cells Ameliorate Osteoarthritis via TNFAIP3-Mediated ChondroprotectionPreprint

Zhuang, Z., Liu, Z., Su, H., Sun, W., Zhu, Q., Xu, J., Fang, J., Li, L., Shen, D., Zou, X., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.12.693855

Infiltration of TIM4-positive intratumoral macrophages serves as an adverse prognostic factor in breast cancer

Yamaguchi, M., Takagi, K., Takahashi, M., Sato, A., Yamazaki, Y., Miyashita, M., & Suzuki, T. (2026) · Breast Cancer · doi:10.1007/s12282-026-01825-8

Mechanistic insights and challenges in mitochondrial regulation of macrophage polarization and inflammatory responses

Liu, X., & Liu, R. (2026) · Frontiers in Physiology · doi:10.3389/fphys.2026.1768672

Ts-Hsp70 confers dual-stage protective immunity against Trichinella spiralis infection by sustaining M1 macrophage polarization in mice

Sun, Q., Huang, J., Gu, Y., Liu, S., Cheng, Y., & Zhu, X. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1799793

Multi-omics analysis identifies NFIL3 as a hypoxia-associated immune regulator in septic cardiomyopathy

Sun, H., Feng, Y., Shao, R., Liu, W., Ren, Z., Hou, X., & He, B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1785241

Targeting CD3L1-NRP2 disarms myeloid-driven tumor immune evasion

Deng, S., Fang, Y., Xue, J., Wang, R., Zhou, X., Li, C., Li, N., Wang, S., Zhang, Y., Wang, H., et al. (2026) · EMBO Molecular Medicine · doi:10.1038/s44321-026-00451-3

HMGB1 down-regulation drives efferocytosis and inflammation suppression: A novel immune adaptation mechanism in Schizopygopsis younghusbandi responding to heat stress

Chen, Z., Wang, J., Jiang, Y., Qin, Z., Wang, N., & Zeng, B. (2026) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2026.111523

Myeloid DRP1 Sulfenylation Drives Reparative Macrophage Polarization and Neovascularization in Ischemic Muscle

Yadav, S., Rajagopal, K., Varadarajan, S., Nagarkoti, S., Das, A., Spears, S. K., Veeranan‐Karmegam, R., Fukai, T., & Ushio‐Fukai, M. (2026) · Antioxidants · doi:10.3390/antiox15060768

Efferocytosis-associated Mrc1+Gas6+ macrophages are linked to abdominal aortic aneurysm progression through ERK-associated dysfunction

Xiang, W., Song, X., Xian, X., Zhou, H., Xu, B., Zhou, L., Yang, D., & Zheng, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1863507

Spasmolytic Polypeptide‐Expressing Metaplasia in Chronic Atrophic Gastritis and Its Role in the Progression From Gastritis to Gastric Cancer

Quan, X., Ji, L., He, T., Liu, J., Shi, L., & Liu, L. (2026) · Journal of Digestive Diseases · doi:10.1111/1751-2980.70060

Non-targeted metabolomics reveals the metabolic atlas of macrophages remodeled by SVPLA2 in Naja atra venom

Li, Q., Chen, S., Wu, J., Tang, S., Wen, Z., Han, X., Bi, X., Huang, C., & Liu, J. (2026) · Toxicon · doi:10.1016/j.toxicon.2026.109226

PFOA promotes PMAIP1–MCL1 apoptotic vulnerability within a BHLHE41-associated macrophage regulatory architecture in atherosclerosis

Chen, H.-L., Wang, R., Tao, W.-J., Zhang, W., Gao, Y.-L., & Cheng, X.-B. (2026) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2026.112265

Macrophage-associated noncoding RNAs in atherosclerosis and chronic kidney disease

Jha, P. K., Nascimento, C. B., Lupieri, A., Aikawa, E. R., & Aikawa, M. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1884576

Meta-inflammation through the lens of macrophage programming and nutrient-sensing ghrelin signaling

Han, H. W., Kim, D. M., Eshghjoo, S., Xu, C., Liu, Z., Patil, B. S., Guo, S., & Sun, Y. (2026) · Immunometabolism · doi:10.1097/in9.0000000000000088

Naja atra SVPLA2 contributes to venom-induced AKI via HRAS palmitoylation-dependent PI3K-AKT inactivation

Liu, J., Chen, S., Wu, J., Tang, S., Wen, Z., Bi, X., Yang, Y., & Huang, C. (2026) · Journal of Lipid Research · doi:10.1016/j.jlr.2026.101123

Impaired Glycolysis Leads to Defective Efferocytosis and Impaired Plaque Resolution in Tet2 Clonal Hematopoiesis

Yalçınkaya, M., Hsu, C.-C., Li, L., Wang, R., Ngai, D., Vela, P. S., Fernández-Maestre, I., Olszewska, M., Liu, W., Chen, M., et al. (2026) · Circulation · doi:10.1161/circulationaha.126.080527

Monotropein mitigates atherosclerotic plaque vulnerability through circ_0140736/miR-495/SIRPα-mediated efferocytosis

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Abandoning M1/M2 for a Network Model of Macrophage Function

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