Macrophage: Biological Functions, Diseases, and Therapeutic Targets

Abstract

Macrophages are sentinel innate immune cells that arise from embryonic precursors and bone marrow monocytes, displaying a functional continuum that transcends the classical M1 (pro-inflammatory)/M2 (anti-inflammatory) dichotomy. Under homeostatic conditions, balanced M1/M2 polarization preserves tissue integrity by coordinating immune surveillance, efferocytosis, and tissue repair. When this equilibrium is disrupted, however, M1-skewed responses drive chronic inflammation and autoimmunity, whereas M2-skewed polarization facilitates tumor immune evasion and organ fibrosis. Although diverse therapeutic strategies—including reprogramming, depletion, blockade of monocyte recruitment, CAR-M cells, and nanomedicine—are being explored to restore homeostasis, clinical translation remains constrained by the lack of pathogenic subset-specific markers, insufficient predictive biomarkers for patient stratification, species divergence between mice and humans, and the temporal complexity of context-dependent intervention windows. In this Review, we systematically delineate macrophage plasticity and the molecular mechanisms underlying polarization imbalance, evaluate existing and emerging macrophage-directed interventions, and dissect these translational bottlenecks in depth, highlighting how single-cell multi-omics, humanized models, and dynamic biomarkers can overcome them. By providing a roadmap for precisely calibrating macrophage functional states and restoring M1/M2 balance, this framework will accelerate the development of precision immunotherapies aimed at re-establishing immune homeostasis across a broad spectrum of human pathologies.

Keywords

M1/M2 activation continuum / M1/M2 imbalance in disease / macrophage polarization / macrophage-targeted therapeutics / tissue-resident macrophages

References

[1] A. Shapouri-Moghaddam, S. Mohammadian, H. Vazini, et al., “Macrophage Plasticity, Polarization, and Function in Health and Disease,” Journal of Cellular Physiology 233, no. 9 (2018): 6425–6440.

[2] M. D. Cooper and M. N. Alder, “The Evolution of Adaptive Immune Systems,” Cell 124, no. 4 (2006): 815–822.

[3] L. Bosurgi, A. A. Manfredi, and P. Rovere-Querini, “Macrophages in Injured Skeletal Muscle: A Perpetuum Mobile Causing and Limiting Fibrosis, Prompting or Restricting Resolution and Regeneration,” Frontiers in immunology 2 (2011): 62.

[4] R. Jin, J. Hao, Y. Yi, E. Sauter, and B. Li, “Regulation of Macrophage Functions by FABP-Mediated Inflammatory and Metabolic Pathways,” Biochimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids 1866, no. 8 (2021): 158964.

[5] S. Verheijden, S. De Schepper, and G. E. Boeckxstaens, “Neuron-Macrophage Crosstalk in the Intestine: A “Microglia” Perspective,” Frontiers in Cellular Neuroscience 9 (2015): 403.

[6] P. Schädel, A. Czapka, N. Gebert, I. D. Jacobsen, A. Ori, and O. Werz, “Metabololipidomic and Proteomic Profiling Reveals Aberrant Macrophage Activation and Interrelated Immunomodulatory Mediator Release During Aging,” Aging Cell 22, no. 7 (2023): e13856.

[7] Y. Wang, X. Lu, J. Lu, P. Hernigou, and F. Jin, “The Role of Macrophage Polarization in Tendon Healing and Therapeutic Strategies: Insights From Animal Models,” Frontiers in Bioengineering and Biotechnology 12 (2024): 1366398.

[8] H. Lu, J. Huang, W. Y. chao, E. Casals, G. Casals, and M. Zeng, “Beyond M1/M2: The Role of Reactive Oxygen Species in Liver Fibrosis and Immune Modulation,” Redox Biology 88 (2025): 103933.

[9] V. M. T. Bart, R. J. Pickering, P. R. Taylor, and N. Ipseiz, “Macrophage Reprogramming for Therapy,” Immunology 163, no. 2 (2021): 128–144.

[10] L. Hui, Y. Li, M. K. Huang, Y. M. Jiang, and T. Liu, “CXCL13: A Common Target for Immune-Mediated Inflammatory Diseases,” Clinical and Experimental Medicine 24, no. 1 (2024): 244.

[11] X. Li, W. Gao, X. Long, and M. Wu, “New Insights Into Monocyte-Derived Macrophages in Glioblastoma,” Research 8 (2025): 0836.

[12] W. Wang, Z. Yi, Z. Yang, et al., “The Hepatic Macrophage: A Key Regulator of Liver Metastatic Tumor Microenvironment Through Cell Crosstalk,” Journal of Translational Medicine 23, no. 1 (2025): 1334.

[13] S. Wang, S. Wang, H. Chen, and J. Xu, “Microglia–Neuron Crosstalk: An Intimate Molecular Conversation in Neurodegeneration,” International Journal of Molecular Sciences 27, no. 4 (2026): 2011.

[14] M. D. Park, A. Silvin, F. Ginhoux, and M. Merad, “Macrophages in Health and Disease,” Cell 185, no. 23 (2022): 4259–4279.

[15] Y. Lavin and M. Merad, “Macrophages: Gatekeepers of Tissue Integrity,” Cancer Immunology Research 1, no. 4 (2013): 201–209.

[16] F. Ginhoux and M. Guilliams, “Tissue-Resident Macrophage Ontogeny and Homeostasis,” Immunity 44, no. 3 (2016): 439–449.

[17] Q. Wang and W. Ma, “Revisiting TAM Polarization: Beyond M1- and M2-type TAM Toward Clinical Precision in Macrophage-targeted Therapy,” Experimental and Molecular Pathology 143 (2025): 104982.

[18] B. Malissen, S. Tamoutounour, and S. Henri, “The Origins and Functions of Dendritic Cells and Macrophages in the Skin,” Nature Reviews Immunology 14, no. 6 (2014): 417–428.

[19] T. Lazarov, S. Juarez-Carreño, N. Cox, and F. Geissmann, “Physiology and Diseases of Tissue-Resident Macrophages,” Nature 618, no. 7966 (2023): 698–707.

[20] M. N. Artyomov, A. Sergushichev, and J. D. Schilling, “Integrating Immunometabolism and Macrophage Diversity,” Seminars in Immunology 28, no. 5 (2016): 417–424.

[21] X. Huang, X. Yang, L. Xiang, and Y. Chen, “Serine Metabolism in Macrophage Polarization,” Inflammation Research Springer Science and Business Media Deutschland GmbH 73, no. 1 (2024): 83–98.

[22] N. Luque-Campos, F. A. Bustamante-Barrientos, C. Pradenas, et al., “The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming,” Frontiers in Immunology 12 (2021): 624746.

[23] T. Zhao, Y. Wang, and F. A. Lin, “Identification of Key Macrophage-Related Genes in Systemic Sclerosis–Associated Interstitial Lung Disease Based on Single-Cell and Bulk Transcriptomic Data,” PLoS ONE 21, no. 3 (2026): e0344166.

[24] S. Härtle, K. Sutton, L. Vervelde, and T. S. Dalgaard, “Delineation of Chicken Immune Markers in the Era of Omics and Multicolor Flow Cytometry,” Frontiers in Veterinary Science 11 (2024): 1385400.

[25] A. A. Filardy, J. R. M. Ferreira, R. M. Rezende, B. L. Kelsall, and R. P. Oliveira, “The Intestinal Microenvironment Shapes Macrophage and Dendritic Cell Identity and Function,” Immunology Letters 253 (2023): 41–53.

[26] D. Y. Guo, Z. Y. Liu, X. C. Xu, et al., “Neutrophil Heterogeneity in Airway Inflammatory Diseases,” Inflammation 48, no. 6 (2025): 3800–3827.

[27] T. Yin, X. Li, Y. Li, X. Zang, L. Liu, and M. Du, “Macrophage Plasticity and Function in Cancer and Pregnancy,” Frontiers in immunology 14 (2024): 1333549.

[28] A. Hassanshahi, M. Moradzad, S. Ghalamkari, M. Fadaei, A. J. Cowin, and M. Hassanshahi, “Macrophage-Mediated Inflammation in Skin Wound Healing,” Cells 11, no. 19 (2022): 2953.

[29] Z. Woolf, M. E. V. Swanson, and L. C. Smyth, “Single-cell Image Analysis Reveals a Protective Role for Microglia in Glioblastoma,” Neuro-Oncology Advances 3, no. 1 (2021): vdab031.

[30] J. Hou, Y. Chen, G. Grajales-Reyes, and M. Colonna, “TREM2 dependent and Independent Functions of Microglia in Alzheimer's Disease,” Molecular Neurodegeneration 17, no. 1 (2022): 84.

[31] K. Man, V. I. Kutyavin, and A. Chawla, “Tissue Immunometabolism: Development, Physiology, and Pathobiology,” Cell Metabolism 25, no. 1 (2017): 11–26.

[32] G. Hoeffel and F. Ginhoux, “Fetal Monocytes and the Origins of Tissue-Resident Macrophages,” Cellular Immunology 330 (2018): 5–15.

[33] R. Watanabe and M. Hashimoto, “Pathogenic Role of Monocytes/Macrophages in Large Vessel Vasculitis,” Frontiers in Immunology 13 (2022): 859502.

[34] F. O. Martinez, T. W. Combes, F. Orsenigo, and S. Gordon, “Monocyte Activation in Systemic Covid-19 Infection: Assay and Rationale,” EBioMedicine 59 (2020): 102964.

[35] N. Xu, B. A. Gonzalez, and K. E. Yutzey, “Macrophage Lineages in Heart Development and Regeneration,” Current Topics in Developmental Biology 156 (2024): 1–17.

[36] B. Kanuri, K. P. Maremanda, D. Chattopadhyay, et al., “Redefining Macrophage Heterogeneity in Atherosclerosis: A Focus on Possible Therapeutic Implications,” Comprehensive Physiology 15, no. 2 (2025): e70008.

[37] H. Ma, M. Zhu, M. Chen, X. Li, and X. Feng, “The Role of Macrophage Plasticity in Neurodegenerative Diseases,” Biomarker Research 12, no. 1 (2024): 81.

[38] C. C. Bain and A. S. MacDonald, “The Impact of the Lung Environment on Macrophage Development, Activation and Function: Diversity in the Face of Adversity,” Mucosal Immunol 15, no. 2 (2022): 223–234.

[39] K. S. Park, Y. J. Ko, and J. H. Choi, “Hypoxia-inducible Factors Link Inflammation and Lipid Metabolism in Atherosclerotic Macrophages,” Frontiers in Cardiovascular Medicine 13 (2026): 1765661.

[40] Y. Chen, Q. Zhu, A. Yin, W. Wang, and J. Wang, “Triptolide-mediated Immunomodulation of Macrophages: From Pathophysiology to Therapy,” Annals of Medicine 57, no. 1 (2025): 2575302.

[41] P. Kolypetri and H. L. Weiner, “Monocyte Regulation by Gut Microbial Signals,” Trends in Microbiology 31, no. 10 (2023): 1044–1057.

[42] J. M. Ortiz Wilczyñski, H. A. Mena, M. M. Ledesma, et al., “The Synthetic Phospholipid C8-C1P Determines Pro-Angiogenic and Pro-Reparative Features in human Macrophages Restraining the Proinflammatory M1-Like Phenotype,” Frontiers in Immunology 14 (2023): 1162671.

[43] R. Gentek, K. Molawi, and M. H. Sieweke, “Tissue Macrophage Identity and Self-Renewal,” Immunological Reviews 262, no. 1 (2014): 56–73.

[44] Y. Sun, J. Li, X. Xie, et al., “Macrophage-Osteoclast Associations: Origin, Polarization, and Subgroups,” Frontiers in Immunology 12 (2021): 778078.

[45] X. Gao, Z. Cao, H. Tan, et al., “LncRNA, an Emerging Approach for Neurological Diseases Treatment by Regulating Microglia Polarization,” Frontiers in Neuroscience 16 (2022): 903472.

[46] D. Chen, J. Hu, M. Zhu, et al., “C-reactive Protein Is a Broad-spectrum Capsule-binding Receptor for Hepatic Capture of Blood-borne Bacteria,” Embo Journal 44, no. 24 (2025): 7364–7394.

[47] L. Rabiller, V. Robert, A. Arlat, et al., “Driving Regeneration, Instead of Healing, in Adult Mammals: The Decisive Role of Resident Macrophages Through Efferocytosis,” NPJ Regenerative Medicine 6, no. 1 (2021): 41.

[48] J. Cao, Y. Zhang, S. Guo, et al., “Immune Biomarkers in Circulating Cells of NSCLC Patients Can Effectively Evaluate the Efficacy of Chemotherapy Combined With Anti-PD-1 Therapy,” Frontiers in Immunology 16 (2025): 1521708.

[49] M. Shojaei, B. Frey, F. Putz, R. Fietkau, U. S. Gaipl, and A. Derer, “Chemoradiation-Altered Micromilieu of Glioblastoma Cells Particularly Impacts M1-Like Macrophage Activation,” International Journal of Molecular Sciences 26, no. 14 (2025): 6574.

[50] O. M. A. Dagah, B. B. Silaa, M. Zhu, et al., “Exploring Immune Redox Modulation in Bacterial Infections: Insights Into Thioredoxin-Mediated Interactions and Implications for Understanding Host–Pathogen Dynamics,” Antioxidants 13, no. 5 (2024): 545.

[51] Y. Zheng, Y. Wang, J. Li, et al., “PGAM5 Modulates Macrophage Polarization, Aggravating Inflammation in COPD via the NF-κB Pathway,” International, Peer-Reviewed Journal of Therapeutics and Pharmacology 20 (2025): 551–564.

[52] M. Hulsmans and M. Nahrendorf, “Smad3 Cranks up the Appetite of Infarct Macrophages,” Circulation Research 125, no. 1 (2019): 71–73.

[53] C. Zhao, T. X. Medeiros, R. J. Sové, B. H. Annex, and A. S. Popel, “A Data-Driven Computational Model Enables Integrative and Mechanistic Characterization of Dynamic Macrophage Polarization,” Iscience 24, no. 2 (2021): 102112.

[54] M. Zhao, S. Yu, M. Zhang, et al., “Macrophages in Ulcerative Colitis: Immunomodulatory Roles, Phenotypic Switching, and Therapeutic Targeting,” Journal of Innate Immunity 18, no. 1 (2026): 85–103.

[55] X. Xu, D. K. W. Ocansey, B. Pei, et al., “Resveratrol Alleviates DSS-Induced IBD in Mice by Regulating the Intestinal Microbiota-Macrophage-Arginine Metabolism Axis,” European Journal of Medical Research 28, no. 1 (2023): 319.

[56] J. Le, Y. Kulatheepan, and S. Jeyaseelan, “Role of Toll-Like Receptors and Nod-Like Receptors in Acute Lung Infection,” Frontiers in Immunology 14 (2023): 1249098.

[57] F. Jyotsna, J. Ikram, F. Nageeta, et al., “Unlocking the Potential of Immunotherapy in Cardiovascular Disease: A Comprehensive Review of Applications and Future Directions,” Cureus 15, no. 8 (2023): e42790, Published online August 1, 2023.

[58] Z. Liu and W. Xu, “Neutrophil and Macrophage Response in Acinetobacter Baumannii Infection and Their Relationship to Lung Injury,” Frontiers in Cellular and Infection Microbiology 12 (2022): 890511.

[59] Y. Xu, K. Hu, C. Liu, et al., “Eschar Dissolution and the Immunoregulator Effect of Keratinase on Burn Wounds,” Scientific Reports 13, no. 1 (2023): 13238.

[60] P. J. Murray, “Macrophage Polarization,” Annual Review of Physiology 79 (2017): 541–566.

[61] S. Yu, S. Wang, X. Wang, and X. Xu, “The Axis of Tumor-associated Macrophages, Extracellular Matrix Proteins, and Cancer-associated Fibroblasts in Oncogenesis,” Cancer cell international 24, no. 1 (2024): 335.

[62] G. Ma, Z. Zhang, P. Li, et al., “Reprogramming of Glutamine Metabolism and Its Impact on Immune Response in the Tumor Microenvironment,” Cell Communication and Signaling 20, no. 1 (2022): 114.

[63] M. K. Callaway, B. J. Noonan, K. L. Schwertfeger, and P. P. Provenzano, “Extracellular Matrix Architecture Promotes Immunosuppressive Microenvironments in Pancreatic Cancer,” Matrix Biology 141 (2025): 114–126.

[64] M. van Eijk and J. Aerts, “The Unique Phenotype of Lipid-Laden Macrophages,” International Journal of Molecular Sciences 22, no. 8 (2021): 4039.

[65] H. R. Chang, T. Josefs, D. Scerbo, et al., “Role of LpL (Lipoprotein Lipase) in Macrophage Polarization in Vitro and in Vivo,” Arteriosclerosis, Thrombosis, and Vascular Biology 39, no. 10 (2019): 1967–1985.

[66] B. S. Finlin, B. Zhu, C. P. Starnes, R. E. McGehee, C. A. Peterson, and P. A. Kern, “Regulation of Thrombospondin-1 Expression in Alternatively Activated Macrophages and Adipocytes: Role of Cellular Cross Talk and Omega-3 Fatty Acids,” Journal of Nutritional Biochemistry 24, no. 9 (2013): 1571–1579.

[67] H. Duan, L. Jing, J. Xiang, et al., “CD146 Associates With Gp130 to Control a Macrophage Pro-Inflammatory Program That Regulates the Metabolic Response to Obesity,” Advanced Science 9, no. 13 (2022): e2103719.

[68] A. Viola, F. Munari, R. Sánchez-Rodríguez, T. Scolaro, and A. Castegna, “The Metabolic Signature of Macrophage Responses,” Frontiers in Immunology 10, no. JULY (2019): 1462.

[69] R. Y. Ma, A. Black, and B. Z. Qian, “Macrophage Diversity in Cancer Revisited in the Era of Single-Cell Omics,” Trends in Immunology 43, no. 7 (2022): 546–563.

[70] S. K. Wculek, G. Dunphy, I. Heras-Murillo, A. Mastrangelo, and D. Sancho, “Metabolism of Tissue Macrophages in Homeostasis and Pathology,” Cellular & Molecular Immunology 19, no. 3 (2022): 384–408.

[71] M. Yao, M. Li, D. Peng, et al., “Unraveling Macrophage Polarization: Functions, Mechanisms, and “Double-Edged Sword” Roles in Host Antiviral Immune Responses,” International Journal of Molecular Sciences 25, no. 22 (2024): 12078.

[72] S. Z. Berg and J. Berg, “Microbes, Macrophages, and Melanin: A Unifying Theory of Disease as Exemplified by Cancer,” Frontiers in Immunology 15 (2025): 1493978.

[73] Y. Wang, N. Ding, L. Qi, W. Chen, and P. Wu, “Immunopharmacology of Gastric Cancer–Deciphering Immune Cell Subset Responses and Nanoparticle-Mediated Targeting,” Frontiers in Pharmacology 16 (2025): 1611234.

[74] D. A. Hume, S. M. Millard, and A. R. Pettit, “Macrophage Heterogeneity in the Single-Cell Era: Facts and Artifacts,” Blood 142, no. 16 (2023): 1339–1347.

[75] L. Dou, X. Shi, X. He, and Y. Gao, “Macrophage Phenotype and Function in Liver Disorder,” Frontiers in Immunology 10 (2020): 3112.

[76] Z. Fremont-Debaene and S. Faure-Dupuy, “Macrophage Makeover Extreme Viral Edition: Mechanisms of Immune Subversion and Therapeutic Perspectives,” Journal of General Virology 107, no. 2 (2026): 002228.

[77] M. F. Viola and G. Boeckxstaens, “Niche-specific Functional Heterogeneity of Intestinal Resident Macrophages,” Gut 70, no. 7 (2021): 1383–1395.

[78] Q. Zhang, Q. Song, Z. Li, X. Wu, Y. Chen, and H. Lin, “Targeting Fibroblasts in Pathological Bone Formation: Mechanisms and Treatments,” Frontiers in Cell and Developmental Biology 13 (2025): 1612950.

[79] I. Rosa, E. Romano, B. S. Fioretto, and M. Manetti, “Pathophysiologic Implications and Therapeutic Potentials of Telocytes in Multiorgan Fibrosis,” Current Opinion in Rheumatology 38, no. 1 (2026): 26–37.

[80] L. Xu, C. Huang, X. Zheng, et al., “Elevated CD169 Expressing Monocyte/Macrophage Promotes Systemic Inflammation and Disease Progression in Cirrhosis,” Clinical and Experimental Medicine 24, no. 1 (2024): 45.

[81] S. Schuermans, C. Kestens, and P. E. Marques, “Systemic Mechanisms of Necrotic Cell Debris Clearance,” Cell Death & Disease 15, no. 8 (2024): 557.

[82] H. Ishikura, H. Okada, Y. Kin, et al., “Loss of Mechanical Stress Induces Synovitis, Fibrosis and Articular Cartilage Degeneration via Distinct Synovial Cell Subsets,” Scientific Reports 16, no. 1 (2026): 8007.

[83] P. Xia, Y. Qu, Q. Liu, et al., “Identification of Programmed Cell Death-Related Subtypes Reveals Immune Heterogeneity and Therapeutic Divergence in Colon Cancer,” Theranostics 16, no. 9 (2026): 4821–4840.

[84] A. K. Elfstrum, A. S. Bapat, and K. L. Schwertfeger, “Defining and Targeting Macrophage Heterogeneity in the Mammary Gland and Breast Cancer,” Cancer Medicine 13, no. 3 (2024): e7053.

[85] D. Jiang, R. Xiao, J. Bai, et al., “FOLR2+ macrophages in Cancer: Allies or Enemies,” Cell Communication and Signaling 23, no. 1 (2025): 261.

[86] X. Liao, E. Chang, X. Tang, et al., “Cardiac Macrophages Regulate Isoproterenol-Induced Takotsubo-Like Cardiomyopathy,” JCI Insight 7, no. 3 (2022): e156236.

[87] R. Chen, Y. Xie, Z. Chang, et al., “Integration of Single-Cell Sequencing With Machine Learning and Mendelian Randomization Analysis Identifies the NAP1L1 Gene as a Predictive Biomarker for Alzheimer's Disease,” Front Aging Neurosci 16, (2024): 1406160.

[88] M. Locati, G. Curtale, and A. Mantovani, “Diversity, Mechanisms, and Significance of Macrophage Plasticity,” Annual Review of Pathology 15 (2020): 123–147, Published online 2019.

[89] X. Fu, M. Pang, Z. Wang, and H. Wang, “Macrophage Polarization in the Tumor Microenvironment of Hepatocellular Carcinoma: From Mechanistic Insights to Translational Therapies,” Cancer Control 32 (2025): 10732748251406674.

[90] Y. Zhang, X. Yang, T. Wang, et al., “Transcriptomic Profiling Reveals Tissue-Specific and Sex-Dimorphic Lipid Storage in Bufo gargarizans,” BMC Genomics [Electronic Resource] 26, no. 1 (2025): 1028.

[91] A. Hu, L. Sun, H. Lin, Y. Liao, H. Yang, and Y. Mao, “Harnessing Innate Immune Pathways for Therapeutic Advancement in Cancer,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 68.

[92] J. Van den Bossche, L. A. O'Neill, and D. Menon, “Macrophage Immunometabolism: Where Are We (Going)?,” Trends in Immunology 38, no. 6 (2017): 395–406.

[93] S. Yao, Y. Cen, G. Lou, and Y. Liu, “Therapeutic Potentials of Mesenchymal Stem Cells and Their Extracellular Vesicles on Liver Diseases by Modulating Mitochondrial Function of Macrophages,” International Immunopharmacology 165 (2025): 115486.

[94] X. Che, Y. Zhang, X. Chen, et al., “The Lactylation-Macrophage Interplay: Implications for Gastrointestinal Disease Therapeutics,” Frontiers in Immunology 16 (2025): 1608115.

[95] J. Saravia, J. L. Raynor, N. M. Chapman, S. A. Lim, and H. Chi, “Signaling Networks in Immunometabolism,” Cell Research 30, no. 4 (2020): 328–342.

[96] A. C. Boese and S. Kang, “Mitochondrial Metabolism-Mediated Redox Regulation in Cancer Progression,” Redox Biology 42 (2021): 101870.

[97] Y. Zhang, Z. Liu, and H. Sun, “Fetal-Maternal Interactions During Pregnancy: A ‘Three-in-One’ Perspective,” Frontiers in Immunology 14 (2023): 1198430.

[98] S. Yu, J. Fu, J. Wang, et al., “The Influence of Mitochondrial-DNA-Driven Inflammation Pathways on Macrophage Polarization: A New Perspective for Targeted Immunometabolic Therapy in Cerebral Ischemia-Reperfusion Injury,” International Journal of Molecular Sciences 23, no. 1 (2021): 135.

[99] L. Wang, D. Wang, T. Zhang, Y. Ma, X. Tong, and H. Fan, “The Role of Immunometabolism in Macrophage Polarization and Its Impact on Acute Lung Injury/Acute Respiratory Distress Syndrome,” Frontiers in Immunology 14 (2023): 1117548.

[100] L. Sainero-Alcolado, J. Liaño-Pons, M. V. Ruiz-Pérez, and M. Arsenian-Henriksson, “Targeting Mitochondrial Metabolism for Precision Medicine in Cancer,” Cell Death and Differentiation 29, no. 7 (2022): 1304–1317.

[101] Y. Wang, X. Zhang, S. Wang, et al., “Identification of Metabolism-Associated Biomarkers for Early and Precise Diagnosis of Oral Squamous Cell Carcinoma,” Biomolecules 12, no. 3 (2022): 400.

[102] D. S. Koenis, L. Medzikovic, P. B. van Loenen, et al., “Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response Through Transcriptional Reprogramming of Mitochondrial Metabolism,” Cell Reports 24, no. 8 (2018): 2127–2140.e7.

[103] A. Qadeer, A. Ullah, M. Z. Khan, et al., “Extracellular Vesicles Associated Metabolites as Intercellular Signalling Mediators in Disease and Therapy,” Metabolites 16, no. 3 (2026): 207.

[104] S. N. Bess, M. J. Igoe, A. C. Denison, and T. J. Muldoon, “Autofluorescence Imaging of Endogenous Metabolic Cofactors in Response to Cytokine Stimulation of Classically Activated Macrophages,” Cancer & Metabolism 11, no. 1 (2023): 22.

[105] C. Di, X. Chu, P. Chang, et al., “The Roles of Histone H3K18 Lactylation, Acetylation, and Lactylation/Acetylation Ratio as Potential Biomarkers in the Diagnosis and Severity Assessment of Sepsis and Septic Shock,” Infectious Diseases and Therapy 14, no. 12 (2025): 2785–2818.

[106] Y. Zhou, Y. Yuan, X. Yao, et al., “miPEP31 Alleviates Sepsis Development by Regulating Chi3l1-Dependent Macrophage Polarization,” Biology Direct 19, no. 1 (2024): 117.

[107] J. Cheng, Y. Zhang, L. Ma, et al., “Macrophage-Derived Extracellular Vesicles-Coated Palladium Nanoformulations Modulate Inflammatory and Immune Homeostasis for Targeting Therapy of Ulcerative Colitis,” Advanced Science 10, no. 33 (2023): e2304002.

[108] J. Yan and T. Horng, “Lipid Metabolism in Regulation of Macrophage Functions,” Trends in Cell Biology 30, no. 12 (2020): 979–989.

[109] A. J. Mouton, X. Li, M. E. Hall, and J. E. Hall, “Obesity, Hypertension, and Cardiac Dysfunction Novel Roles of Immunometabolism in Macrophage Activation and Inflammation,” Circulation Research 126, no. 6 (2020): 789–806.

[110] F. Vinchi, “Macrophage-Based Cell Strategies: A Novel Approach in Immunotherapy,” Hemasphere 6, no. 2 (2022): e682.

[111] X. Chen, C. Lai, L. Cai, and L. Huang, “Cross One Single Body 49 Tissues Single-Cell Transcriptome Reveals Detailed Macrophage Heterogeneity During Pig Pregnancy,” Frontiers in Immunology 16 (2025): 1574120.

[112] J. Bonnardel and M. Guilliams, “Developmental Control of Macrophage Function,” Current Opinion in Immunology 50 (2018): 64–74.

[113] E. Boada-Romero, J. Martinez, B. L. Heckmann, and D. R. Green, “The Clearance of Dead Cells by Efferocytosis,” Nature Reviews Molecular Cell Biology 21, no. 7 (2020): 398–414.

[114] C. Chen, J. Wang, C. Liu, and J. Hu, “Cardiac Resident Macrophages: Key Regulatory Mediators in the Aftermath of Myocardial Infarction,” Frontiers in Immunology 14 (2023): 1207100.

[115] R. Pandit and A. Yurdagul, “The Atherosclerotic Plaque Microenvironment as a Therapeutic Target,” Current Atherosclerosis Reports 27, no. 1 (2025): 47.

[116] P. Sun, S. Liu, Q. Zeng, et al., “The Regulatory Mechanisms of Treponema pallidum Enolase on Macrophages: From Enzymatic Activity to Signal Transduction,” The FASEB Journal 39, no. 13 (2025): e70801.

[117] H. Li, B. Sun, X. Ning, S. Jiang, and L. Sun, “A Comparative Analysis of Edwardsiella Tarda-Induced Transcriptome Profiles in RAW264.7 Cells Reveals New Insights Into the Strategy of Bacterial Immune Evasion,” International Journal of Molecular Sciences 20, no. 22 (2019): 5724.

[118] J. Correale and E. Carnero Contentti, “Induction of Immune Tolerance in NMOSD and MOGAD,” Therapeutic Advances in Neurological Disorders 18 (2025): 17562864251357393.

[119] H. Shah, Z. Liu, W. Guo, W. Ren, and Y. Xiao, “Immune-Regulating Extracellular Vesicles: A New Frontier in Autoimmune Disease Therapy,” Essays in Biochemistry 69, no. 02 (2025): 161–168.

[120] R. Huang, T. Kang, and S. Chen, “The Role of Tumor-Associated Macrophages in Tumor Immune Evasion,” Journal of Cancer Research and Clinical Oncology 150, no. 5 (2024): 238.

[121] K. M. Sheu and A. Hoffmann, “Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance,” Annual Review of Immunology 40 (2022): 295–321.

[122] M. K. Khoury, H. Yang, and B. Liu, “Macrophage Biology in Cardiovascular Diseases,” Arteriosclerosis, Thrombosis, and Vascular Biology 41, no. 2 (2021): E77–E81.

[123] F. Geissmann and E. Mass, “A Stratified Myeloid System, the Challenge of Understanding Macrophage Diversity,” Seminars in Immunology 27, no. 6 (2015): 353–356.

[124] E. R. Stevenson, L. C. Smith, M. L. Wilkinson, S. J. Lee, and A. J. Gow, “Etiology of Lipid-Laden Macrophages in the Lung,” International Immunopharmacology 123 (2023): 110719.

[125] J. Kang, P. Hua, X. Wu, and B. Wang, “Exosomes: Efficient Macrophage-Related Immunomodulators in Chronic Lung Diseases,” Frontiers in Cell and Developmental Biology 12 (2024): 1271684.

[126] G. I. Soma, M. Oda, V. T. Tjhin, C. Kohchi, and H. Inagawa, “Oral and Transdermal Administration of Lipopolysaccharide Safely Enhances Self-Healing Ability Through the Macrophage Network,” Frontiers in Immunology 16 (2025): 1563484.

[127] P. R. Taylor, L. Martinez-Pomares, M. Stacey, H. H. Lin, G. D. Brown, and S. Gordon, “Macrophage Receptors and Immune Recognition,” Annual Review of Immunology 23 (2005): 901–944.

[128] S. Yadav, A. Priya, D. R. Borade, and R. Agrawal-Rajput, “Macrophage Subsets and Their Role: Co-Relation With Colony-Stimulating Factor-1 Receptor and Clinical Relevance,” Immunologic Research 71, no. 2 (2023): 130–152.

[129] Y. Q. Liu, Z. Z. Li, Y. L. Han, and Q. B. Wang, “The Role of Efferocytosis in Inflammatory Bowel Disease,” Frontiers in Immunology 16 (2025): 1524058.

[130] H. Pan, J. Liu, Y. Dong, et al., “Release of Prostaglandin E₁ From N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates by Bone Cells,” Macromolecular Bioscience 8, no. 7 (2008): 599–605.

[131] S. De Schepper, S. Verheijden, J. Aguilera-Lizarraga, et al., “Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis,” Cell 175, no. 2 (2018): 400–415.e13.

[132] D. Lanjewar, R. Katariya, V. Kale, B. Taksande, M. Umekar, and M. Vinchurney, “Interplay of Neuropeptide Y and Autophagy in Alzheimer's Disease: Therapeutic Perspectives and Mechanistic Insights,” Neuropeptides 113 (2025): 102547.

[133] A. F. M. Salvador, N. Abduljawad, and J. Kipnis, “Meningeal Lymphatics in Central Nervous System Diseases,” Annual Review of Neuroscience 47, no. 1 (2024): 323–344.

[134] T. Zhao, Q. Jiang, W. Li, et al., “Antigen-Presenting Cell-Like Neutrophils Foster T Cell Response in Hyperlipidemic Patients and Atherosclerotic Mice,” Frontiers in Immunology 13 (2022): 851713.

[135] S. N. Karagiannis, D. H. Josephs, H. J. Bax, and J. F. Spicer, “Therapeutic IgE Antibodies: Harnessing a Macrophage-Mediated Immune Surveillance Mechanism Against Cancer,” Cancer Research 77, no. 11 (2017): 2779–2783.

[136] T. T. He, P. Y. Tang, X. L. Jiang, S. S. Sun, P. Nie, and H. X. Xie, “T3SS effector EseJ in Edwardsiella piscicida Inhibits PANoptosis in Macrophages,” Communications Biology 8, no. 1 (2025): 1420.

[137] S. K. Tiwary, T. Hayashi, A. Kovacs, and D. L. Mann, “Recurrent Myocardial Injury Leads to Disease Tolerance in a Murine Model of Stress-Induced Cardiomyopathy,” JACC: Basic to Translational Science 8, no. 7 (2023): 783–797.

[138] S. Dyckhoff-Shen, I. Masouris, H. W. Pfister, et al., “Pharmacologic Depletion of Border-Associated Macrophages Worsens Disease in a Mouse Model of Meningitis,” Acta Neuropathologica Communications 13, no. 1 (2025): 191.

[139] A. Chavda, X. Zhou, M. A. Tokmedash, J. J. Moon, and J. Min, “Tunable Wrinkled Topographies Direct Dendritic Cell Maturation and Immune Phenotypes,” Acta Biomaterialia 212 (2026): 428–443.

[140] N. Luo, G. Yang, P. Zhang, et al., “Development of an Early Mortality Risk Prediction Model for Pediatric Patients With Secondary Hemophagocytic Lymphohistiocytosis,” Italian Journal of Pediatrics 51, no. 1 (2025): 221.

[141] P. Wielgat, K. Narejko, and H. Car, “SARS-CoV-2 Attacks in the Brain: Focus on the Sialome,” Cells 11, no. 9 (2022): 1458.

[142] I. M. De la Fuente, J. Carrasco-Pujante, M. Fedetz, et al., “Migratory Responses in Enucleated Cells: The Forces Driving the Locomotion Movement of Unicellular Organisms,” PNAS Nexus 4, no. 8 (2025): pgaf232.

[143] F. Constanty, B. Wu, K. H. Wei, et al., “Border-zone Cardiomyocytes and Macrophages Regulate Extracellular Matrix Remodeling to Promote Cardiomyocyte Protrusion During Cardiac Regeneration,” Nature Communications 16, no. 1 (2025): 3823.

[144] D. Moreno-Blas, T. Adell, and C. González-Estévez, “Autophagy in Tissue Repair and Regeneration,” Cells 14, no. 4 (2025): 282.

[145] H. Li, Q. Zhu, W. Wang, et al., “Identification of Biomarkers Associated With M1 Macrophages in the ST-segment Elevation Myocardial Infarction Through Bioinformatics and Machine Learning Approaches,” Scientific Reports 15, no. 1 (2025): 11069.

[146] T. D. Smith, R. R. Nagalla, E. Y. Chen, and W. F. Liu, “Harnessing Macrophage Plasticity for Tissue Regeneration,” Advanced Drug Delivery Reviews 114 (2017): 193–205.

[147] T. A. Wynn and K. M. Vannella, “Macrophages in Tissue Repair, Regeneration, and Fibrosis,” Immunity 44, no. 3 (2016): 450–462.

[148] P. Huebener and R. F. Schwabe, “Regulation of Wound Healing and Organ Fibrosis by Toll-Like Receptors,” Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease 1832, no. 7 (2013): 1005–1017.

[149] S. Watanabe, M. Alexander, A. V. Misharin, and G. R. S. Budinger, “The Role of Macrophages in the Resolution of Inflammation,” Journal of Clinical Investigation 129, no. 7 (2019): 2619–2628.

[150] Y. Zheng, Y. Han, Q. Sun, and Z. Li, “Harnessing Anti-Tumor and Tumor-Tropism Functions of Macrophages via Nanotechnology for Tumor Immunotherapy,” Exploration 2, no. 3 (2022): 20210166.

[151] Z. Liu, Y. Li, Y. Ren, et al., “Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate,” Aging Cell 24, no. 2 (2025): e14467.

[152] J. Luo, Q. Lian, D. Zhu, et al., “PLSCR1 Promotes Apoptosis and Clearance of Retinal Ganglion Cells in Glaucoma Pathogenesis,” Genes & Diseases 10, no. 4 (2023): 1564–1581.

[153] N. Karaji and Q. J. Sattentau, “Efferocytosis of Pathogen-Infected Cells,” Frontiers in Immunology 8 (2017): 1863.

[154] B. L. Heckmann, E. Boada-Romero, L. D. Cunha, J. Magne, and D. R. Green, “LC3-Associated Phagocytosis and Inflammation,” Journal of Molecular Biology 429, no. 23 (2017): 3561–3576.

[155] B. Krenz, J. Lee, T. Kannan, and M. Eilers, “Immune Evasion: An Imperative and Consequence of MYC Deregulation,” Molecular Oncology 18, no. 10 (2024): 2338–2355, Published online July 2, 2024.

[156] H. Li, A. Wang, Y. Zhang, and F. Wei, “Diverse Roles of Lung Macrophages in the Immune Response to Influenza A Virus,” Frontiers in Microbiology 14 (2023): 1260543.

[157] R. Siebeler, M. P. J. de Winther, and M. A. Hoeksema, “The Regulatory Landscape of Macrophage Interferon Signaling in Inflammation,” Journal of Allergy and Clinical Immunology 152, no. 2 (2023): 326–337.

[158] M. Shu, M. Fang, T. Xu, and Q. Yan, “Functional Roles and Regulatory Mechanisms of Paeonol in the Treatment of Liver Disease,” Natural Products and Bioprospecting 16, no. 1 (2026): 2.

[159] Y. Wang, X. Y. Liu, Y. Wang, et al., “NOX2 inhibition Stabilizes Vulnerable Plaques by Enhancing Macrophage Efferocytosis via MertK/PI3K/AKT Pathway,” Redox Biology 64 (2023): 102763.

[160] D. Sokolova, T. Childs, and S. Hong, “Insight Into the Role of Phosphatidylserine in Complement-Mediated Synapse Loss in Alzheimer's Disease,” Faculty Reviews 10 (2021): 19.

[161] C. Gupta, J. Xu, T. Jin, et al., “Single-Cell Network Biology Characterizes Cell Type Gene Regulation for Drug Repurposing and Phenotype Prediction in Alzheimer's Disease,” Plos Computational Biology 18, no. 7 (2022): e1010287.

[162] R. A. Campbell, M. H. Docherty, D. A. Ferenbach, and K. J. Mylonas, “The Role of Ageing and Parenchymal Senescence on Macrophage Function and Fibrosis,” Frontiers in Immunology 12 (2021): 700790.

[163] G. Urbani, E. Rondini, E. Distrutti, S. Marchianò, M. Biagioli, and S. Fiorucci, “Phenotyping the Chemical Communications of the Intestinal Microbiota and the Host: Secondary Bile Acids as Postbiotics,” Cells 14, no. 8 (2025): 595.

[164] J. Ghebrehiwet-Kuflom, A. Mehta, P. Lim, S. Dahle, and R. R. Isseroff, “GLP-1 Receptor Agonists as Emerging Modulators of Inflammation and Angiogenesis in Chronic Cutaneous Wound Healing,” Journal of Investigative Dermatology 145, no. 12 (2025): 2981–2988.

[165] E. A. Kim, N. Kang, J. Kim, H. W. Yang, G. Ahn, and S. J. Heo, “Anti-Inflammatory Effect of Turbo Cornutus Viscera Ethanolic Extract Against Lipopolysaccharide-Stimulated Inflammatory Response via the Regulation of the JNK/NF-kB Signaling Pathway in Murine Macrophage RAW 264.7 Cells and a Zebrafish Model: A Preliminary Study,” Foods 11, no. 3 (2022): 364.

[166] N. Suttawong, N. Witayavanitkul, M. Chayanupatkul, et al., “Gardenia jasminoides Fruit Extract Ameliorates Non-Alcoholic Steatohepatitis With Fibrosis by Modulating Inflammatory and Fibrogenic Pathways,” PLoS ONE 20, no. 10 (2025): e0333800.

[167] C. Maruyama, M. Uchiyama, A. Umezawa, et al., “A Cross-Sectional Pilot Study on Association of Ready-to-Eat and Processed Food Intakes With Metabolic Factors, Serum Trans Fat and Phospholipid Fatty Acid Compositions in Healthy Japanese Adults,” Nutrients 16, no. 7 (2024): 1032.

[168] B. Burja, D. Paul, A. Tastanova, et al., “An Optimized Tissue Dissociation Protocol for Single-Cell RNA Sequencing Analysis of Fresh and Cultured Human Skin Biopsies,” Frontiers in Cell and Developmental Biology 10 (2022): 872688.

[169] X. Zhang, L. Ji, and M. O. Li, “Control of Tumor-associated Macrophage Responses by Nutrient Acquisition and Metabolism,” Immunity 56, no. 1 (2023): 14–31.

[170] Q. Zhou, C. Xue, J. Man, et al., “Correlation of Tumor-Associated Macrophage Infiltration in Glioblastoma With Magnetic Resonance Imaging Characteristics: A Retrospective Cross-Sectional Study,” Quantitative Imaging in Medicine and Surgery 13, no. 9 (2023): 5958–5973.

[171] K. Wu, K. Lin, X. Li, et al., “Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment,” Frontiers in Immunology 11 (2020): 1731.

[172] Y. Pan, Y. Yu, X. Wang, and T. Zhang, “Tumor-Associated Macrophages in Tumor Immunity,” Frontiers in Immunology 11 (2020): 583084.

[173] Q. Zhang, Y. Wei, Y. Li, and X. Jiao, “Low MARCO Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma Following Liver Transplantation,” Cancer Management and Research 14 (2022): 1935–1944.

[174] Y. Shao and B. Lu, “The Crosstalk Between Circular RNAs and the Tumor Microenvironment in Cancer Metastasis,” Cancer Cell International 20, no. 1 (2020): 448.

[175] X. Bai, Y. R. Guo, Z. M. Zhao, et al., “Macrophage Polarization in Cancer and Beyond: From Inflammatory Signaling Pathways to Potential Therapeutic Strategies,” Cancer Letters 625 (2025): 217772.

[176] H. Wang, X. Wang, X. Zhang, and W. Xu, “The Promising Role of Tumor-Associated Macrophages in the Treatment of Cancer,” Drug Resistance Updates 73 (2024): 101041.

[177] N. R. Anderson, N. G. Minutolo, S. Gill, and M. Klichinsky, “Macrophage-Based Approaches for Cancer Immunotherapy,” Cancer Research 81, no. 5 (2021): 1201–1208.

[178] W. Hou, B. Yang, and H. Zhu, “Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy,” Pharmaceutics 14, no. 10 (2022): 2033.

[179] T. Xia, M. Zhang, W. Lei, et al., “Advances in the Role of STAT3 in Macrophage Polarization,” Frontiers in Immunology 14 (2023): 1160719.

[180] K. Pomeyie, F. Abrokwah, D. Boison, et al., “Macrophage Immunometabolism Dysregulation and Inflammatory Disorders,” Biomedicine and Pharmacotherapy 188 (2025): 118142.

[181] S. Wu, S. Zhao, L. Hai, et al., “Macrophage Polarization Regulates the Pathogenesis and Progression of Autoimmune Diseases,” Autoimmunity Reviews 24, no. 7 (2025): 103820.

[182] M. Kurowska-Stolarska and S. Alivernini, “Synovial Tissue Macrophages in Joint Homeostasis, Rheumatoid Arthritis and Disease Remission,” Nature Reviews Rheumatology 18, no. 7 (2022): 384–397.

[183] K. Kulakova, T. R. Lawal, E. Mccarthy, and A. Floudas, “The Contribution of Macrophage Plasticity to Inflammatory Arthritis and Their Potential as Therapeutic Targets,” Cells 13, no. 18 (2024): 1586.

[184] E. Keewan and S. A. Naser, “The Role of Notch Signaling in Macrophages During Inflammation and Infection: Implication in Rheumatoid Arthritis?,” Cells 9, no. 1 (2020): 111.

[185] S. Semenistaja, S. Skuja, A. Kadisa, and V. Groma, “Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk,” International Journal of Molecular Sciences 24, no. 4 (2023): 4120.

[186] K. Zhang, J. Guo, W. Yan, and L. Xu, “Macrophage Polarization in Inflammatory Bowel Disease,” Cell Communication and Signaling 21, no. 1 (2023): 367.

[187] Y. Zheng, Y. Yu, X. F. Chen, S. L. Yang, X. L. Tang, and Z. G. Xiang, “Intestinal Macrophage Autophagy and Its Pharmacological Application in Inflammatory Bowel Disease,” Frontiers in Pharmacology 12 (2021): 803686.

[188] E. J. Wang, M. Y. Wu, Z. Y. Ren, et al., “Targeting Macrophage Autophagy for Inflammation Resolution and Tissue Repair in Inflammatory Bowel Disease,” Burns Trauma 11 (2023): tkad004.

[189] Y. Zheng, K. Wei, P. Jiang, et al., “Macrophage Polarization in Rheumatoid Arthritis: Signaling Pathways, Metabolic Reprogramming, and Crosstalk With Synovial Fibroblasts,” Frontiers in Immunology 15 (2024): 1394108.

[190] X. Fang, J. Yang, L. Yang, et al., “Multi-omics Analysis Identified Macrophages as Key Contributors to Sex-related Differences in Ulcerative Colitis,” Frontiers in Immunology 16 (2025): 1569271.

[191] Y. Cui, J. Chen, Z. Zhang, H. Shi, W. Sun, and Q. Yi, “The Role of AMPK in Macrophage Metabolism, Function and Polarisation,” Journal of Translational Medicine 21, no. 1 (2023): 892.

[192] M. Appari, K. M. Channon, and E. McNeill, “Metabolic Regulation of Adipose Tissue Macrophage Function in Obesity and Diabetes,” Antioxid Redox Signaling 29, no. 3 (2018): 297–312.

[193] D. Thomas and C. Apovian, “Macrophage Functions in Lean and Obese Adipose Tissue,” Metabolism 72 (2017): 120–143.

[194] L. Ménégaut, A. Jalil, C. Thomas, and D. Masson, “Macrophage Fatty Acid Metabolism and Atherosclerosis: The Rise of PUFAs,” Atherosclerosis 291 (2019): 52–61.

[195] T. Chavakis, V. I. Alexaki, and A. W. Ferrante, “Macrophage Function in Adipose Tissue Homeostasis and Metabolic Inflammation,” Nature Immunology 24, no. 5 (2023): 757–766.

[196] M. X. Wu, I. V. Ustyugova, L. Han, and O. E. Akilov, “Immediate Early Response Gene X-1, a Potential Prognostic Biomarker in Cancers,” Expert Opinion on Therapeutic Targets 17, no. 5 (2013): 593–606.

[197] D. Liddle, A. Hutchinson, H. Wellings, K. Power, L. Robinson, and J. Monk, “Integrated Immunomodulatory Mechanisms Through Which Long-Chain n-3 Polyunsaturated Fatty Acids Attenuate Obese Adipose Tissue Dysfunction,” Nutrients 9, no. 12 (2017): 1289.

[198] A. D. Ruggiero, C. C. C. Key, and K. Kavanagh, “Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity,” Frontiers in Nutrition 8 (2021): 625331.

[199] K. Drareni, J. F. Gautier, N. Venteclef, and F. Alzaid, “Transcriptional Control of Macrophage Polarisation in Type 2 Diabetes,” Seminars in Immunopathology 41, no. 4 (2019): 515–529.

[200] M. Ahmed, M. P. J. de Winther, and J. Van den Bossche, “Epigenetic Mechanisms of Macrophage Activation in Type 2 Diabetes,” Immunobiology 222, no. 10 (2017): 937–943.

[201] J. Fang, Y. Wu, H. Wang, J. Zhang, and L. You, “Oral Health and Diabetic Cardiomyopathy: Mechanisms, Biomarkers, and Early Screening Approaches,” Journal of Inflammation Research 18 (2025): 8689–8704.

[202] W. Sheng, G. Ji, and L. Zhang, “Role of Macrophage Scavenger Receptor MSR1 in the Progression of Non-Alcoholic Steatohepatitis,” Frontiers in Immunology 13 (2022): 1050984.

[203] A. Adnan, M. Juntunen, and T. Tyrväinen, “Effects of Bariatric Surgery-Related Weight Loss on the Characteristics, Metabolism, and Immunomodulation of Adipose Stromal/Stem Cells in a Follow-Up Study,” Stem Cells International 2025, no. 1 (2025): 1212255.

[204] J. Q. Ban, L. H. Ao, X. He, H. Zhao, and J. Li, “Advances in Macrophage-Myofibroblast Transformation in Fibrotic Diseases,” Frontiers in Immunology 15 (2024): 1461919.

[205] B. W. Zhou, H. M. Liu, F. Xu, and X. H. Jia, “The Role of Macrophage Polarization and Cellular Crosstalk in the Pulmonary Fibrotic Microenvironment: A Review,” Cell Communication and Signaling 22, no. 1 (2024): 172.

[206] L. Bertran, A. Eigbefoh-Addeh, M. Portillo-Carrasquer, et al., “Identification of the Potential Molecular Mechanisms Linking RUNX1 Activity With Nonalcoholic Fatty Liver Disease, by Means of Systems Biology,” Biomedicines 10, no. 6 (2022): 1315.

[207] W. L. Xun, Z. S. Xi, W. H. Juan, R. X. Lu, and J. Guo, “M2b macrophage Polarization and Its Roles in Diseases,” Journal of Leukocyte Biology 106, no. 2 (2019): 345–358.

[208] C. Wang, C. Ma, L. Gong, et al., “Macrophage Polarization and Its Role in Liver Disease,” Frontiers in Immunology 12 (2021): 803037.

[209] M. M. Aychman, D. L. Goldman, and J. S. Kaplan, “Cannabidiol's Neuroprotective Properties and Potential Treatment of Traumatic Brain Injuries,” Frontiers in Neurology 14 (2023): 1087011.

[210] S. Yu, D. Kong, B. Lu, et al., “Mesenchymal Stem Cell-Derived Exosomes as Cell-Free Therapeutics: Mechanistic Insights and Engineering Strategies for Liver Disease Treatment,” Stem Cell Research & Therapy 16, no. 1 (2025): 652.

[211] D. Zhou, K. Yang, L. Chen, et al., “Macrophage Polarization and Function: New Prospects for Fibrotic Disease,” Immunology and Cell Biology 95, no. 10 (2017): 864–869.

[212] C. Atri, F. Z. Guerfali, and D. Laouini, “Role of human Macrophage Polarization in Inflammation During Infectious Diseases,” International Journal of Molecular Sciences 19, no. 6 (2018): 1801.

[213] G. A. Duque and A. Descoteaux, “Macrophage Cytokines: Involvement in Immunity and Infectious Diseases,” Frontiers in Immunology 5, no. OCT (2014): 491.

[214] V. Torraca, S. Masud, H. P. Spaink, and A. H. Meijer, “Macrophage-Pathogen Interactions in Infectious Diseases: New Therapeutic Insights From the Zebrafish Host Model,” DMM Disease Models and Mechanisms 7, no. 7 (2014): 785–797.

[215] R. Chen, H. Zhang, B. Tang, et al., “Macrophages in Cardiovascular Diseases: Molecular Mechanisms and Therapeutic Targets,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 130.

[216] S. Chen, A. Saeed, Q. Liu, et al., “Macrophages in Immunoregulation and Therapeutics,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 207.

[217] M. Holterhus, B. Altvater, S. Kailayangiri, and C. Rossig, “The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies,” Cancers (Basel) 14, no. 9 (2022): 2177.

[218] A. L. Garfall, A. D. Cohen, S. P. Susanibar-Adaniya, et al., “Anti-BCMA/CD19 CAR T Cells With Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy,” Blood Cancer Discovery 4, no. 2 (2023): 118–133.

[219] M. Shi, H. Yuan, Y. Li, Z. Guo, and J. Wei, “Targeting Macrophage Phenotype for Treating Heart Failure: A New Approach,” Drug Design, Development and Therapy 18 (2024): 4927–4942.

[220] G. Liu, Y. Dai, C. Fu, X. Lv, J. Qin, and J. Xie, “Macrophage Polarization in Myocardial Ischemia-Reperfusion Injury: Pathophysiology and Therapeutic Targets,” Drug Design, Development and Therapy 19 (2025): 6519–6541.

[221] C. Chen, R. Wang, X. Chen, Y. Hou, and J. Jiang, “Targeting CD47 as a Novel Immunotherapy for Breast Cancer,” Frontiers in Oncology 12 (2022): 924740.

[222] G. Huang and D. Li, “The Macrophage Opera: From Metabolic Prolog to Oncogenic Crescendo in Metabolic Dysfunction-Associated Steatotic Liver Disease,” Frontiers in Medicine 13 (2026): 1751290.

[223] F. Ingelfinger, S. Krishnarajah, M. Kramer, et al., “Single-Cell Profiling of Myasthenia Gravis Identifies a Pathogenic T Cell Signature,” Acta Neuropathologica 141, no. 6 (2021): 901–915.

[224] A. Ellert-Miklaszewska, P. Pilanc, K. Poleszak, et al., “7aaRGD—a Novel SPP1/Integrin Signaling-Blocking Peptide Reverses Immunosuppression and Improves anti-PD-1 Immunotherapy Outcomes in Experimental Gliomas,” Journal of Experimental & Clinical Cancer Research 44, no. 1 (2025): 132.

[225] J. Li, X. Jiang, H. Li, M. Gelinsky, and Z. Gu, “Tailoring Materials for Modulation of Macrophage Fate,” Advanced Materials 33, no. 12 (2021): e2004172.

[226] M. Dahri, M. Rezaeian, H. Sadeghzadeh, et al., “Nanomaterial-Driven Macrophage Polarization: Emerging Strategies for Immunomodulation and Regenerative Medicine,” Biomedicine and Pharmacotherapy 190 (2025): 118360.

[227] X. Miao, X. Leng, and Q. Zhang, “The Current state of Nanoparticle-induced Macrophage Polarization and Reprogramming Research,” International Journal of Molecular Sciences 18, no. 2 (2017): 336.

[228] M. Santoni, F. Massari, R. Montironi, and N. Battelli, “Manipulating Macrophage Polarization in Cancer Patients: From Nanoparticles to Human Chimeric Antigen Receptor Macrophages,” Biochimica Et Biophysica Acta-Reviews on Cancer 1876, no. 1 (2021): 188547.

[229] R. Cui, J. Zhou, W. Yang, et al., “Ultrasound-Triggered Nanogel Boosts Chemotherapy and Immunomodulation in Colorectal Cancer,” ACS Applied Materials & Interfaces 17, no. 1 (2025): 211–221.

[230] Z. Fu, X. Zhao, Q. Zhang, et al., “Synthetic SIGLEC9-based Chimeric Switch Receptor Augments the Efficacy of CAR Macrophages Against Glioblastoma,” Proceedings of the National Academy of Sciences 123, no. 12 (2026): e2519819123.

[231] J. Jing, Y. Chen, and E. Chi, “New Power in Cancer Immunotherapy: The Rise of Chimeric Antigen Receptor Macrophage (CAR-M),” Journal of Translational Medicine 23, No. 1 (2025): 1182.

[232] J. Wei, Y. Dai, N. Zhang, et al., “Natural Plant-derived Polysaccharides Targeting Macrophage Polarization: A Promising Strategy for Cancer Immunotherapy,” Frontiers in immunology 15 (2024): 1408377.

[233] K. R. Peterson, M. A. Cottam, A. J. Kennedy, and A. H. Hasty, “Macrophage-Targeted Therapeutics for Metabolic Disease,” Trends in Pharmacological Sciences 39, no. 6 (2018): 536–546.

[234] D. H. Kang, Y. Kim, J. H. Lee, H. S. Kang, and C. Chung, “Spatial Transcriptomics in Lung Cancer and Pulmonary Diseases: A Comprehensive Review,” Cancers (Basel) 17, no. 12 (2025): 1912.

Rights & permissions

2026 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.