Macrophage
Macrophages are mononuclear phagocytes with two distinct origins: circulating monocytes recruited into tissue, and embryonic and fetal progenitors that seed tissues before birth.
Macrophages are mononuclear phagocytes with two distinct origins: circulating monocytes recruited into tissue, and embryonic and fetal progenitors that seed tissues before birth. The resident populations founded by the second route — microglia in the brain, Kupffer cells in the liver, alveolar macrophages in the lung — largely maintain themselves by local self-renewal rather than by monocyte replacement, which is why their behavior is set as much by tissue niche as by lineage. Macrophage identity is defined by a combination of markers such as CD68, CD64 and MERTK rather than by any single one; CD11b is shared with neutrophils and other myeloid cells, and is also expressed by natural killer cells and some lymphocytes, so it does not distinguish myeloid from non-myeloid cells. Activation is conventionally described as a spectrum between M1 (pro-inflammatory) and M2 (anti-inflammatory, tissue-remodeling) states, a shorthand drawn from cultured cells that remains useful for orientation, though macrophages in tissue occupy stimulus-specific states that do not resolve cleanly onto that axis.
Their core functions are phagocytosis of pathogens and debris, clearance of apoptotic cells, antigen presentation to T-lymphocytes, and secretion of the cytokines and chemokines that recruit and instruct other cells. Clearance of dying cells is not merely disposal: it actively signals resolution, shifting the macrophage toward a reparative program and terminating inflammation. Through the same machinery macrophages handle iron and lipid — recycling iron from senescent erythrocytes, and taking up modified lipoproteins in the artery wall, where sustained uptake converts them into the foam cells of atherosclerotic plaque. They act as integrators within immune networks, exchanging signals with dendritic cell populations, T lymphocytes, and natural killer cell populations to shape both innate and adaptive responses.
That same plasticity makes them a therapeutic target from both directions. In chronic inflammatory disease such as rheumatoid arthritis and atherosclerosis, macrophages sustain pathology through oxidative stress and tissue damage, and the goal is to repolarize them toward resolution. In cancer, tumor-associated macrophages (TAMs) are among the most abundant cells of the tumor microenvironment, where they suppress T cell responses, promote angiogenesis, and support metastasis; reprogramming them toward an inflammatory, anti-tumor phenotype is an active immunotherapy strategy. Their appetite for particulate material cuts both ways in drug delivery: it clears nanoparticles from circulation before they reach their target, and it also makes the macrophage itself an addressable one.
Where the papers sit
18 papers from the last 6 months study macrophage directly · updated from PubMed 12 Oct 2026
Study type 0 clinical trials · 16 preclinical · 2 unclassified
Themes 4 themes · 1 paradigm shift
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Macrophage Roles in Tissue Injury
Liver injury, MASH, fibrosis and wound repair are being framed as context-dependent macrophage problems. Proposed interventions modulate efferocytosis, autophagy, PI3Kγ or macrophage abundance using GPR91 pathways, hydrogels, liposomes and mannose-modified vectors. Macrophage inflammatory signals also connect diabetic kidney disease, pulmonary fibrosis, tumors and vaccine granulomas. The recurring challenge is to suppress pathogenic inflammation without losing macrophage functions needed for repair.
9 papers · 50%
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Spatial Mapping of Macrophage States
Spatially resolved profiling is defining macrophage states within immunosuppressed tumors and regenerating tissues. Single-cell multi-omics, spatial biology and CRISPR screen sequencing connect macrophages to fibroblasts and SFRP4+ stroma. In cancer, these maps are being paired with TAM-targeted nanomedicine rather than treating macrophages as a uniform population. The open issue is whether spatially identified interactions can yield durable immune reprogramming in patients.
4 papers · 22.2%
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Macrophage Ferroptosis in Disease
Macrophage ferroptosis is emerging as a therapeutic target across sepsis and vascular disease. FAR1 inhibition, including repurposed irinotecan, is proposed to protect against intestinal macrophage ferroptosis in sepsis. In atherosclerosis, MCL acts through NRF2/HO-1/GPX4 to limit lipid damage and plaque formation. Lipid lowering, ferroptosis control and nanomedicine are converging, but the safest intervention point remains unresolved.
3 papers · 16.7%
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Macrophage Polarization in Inflammation
Macrophage glycolysis and polarization are being targeted to reduce inflammatory disease. Indole-pyridine chalcones inhibit HK2, linking metabolic rewiring to anti-inflammatory macrophage programs. Zhiwang decoction acts through PI3K/AKT phosphorylation in rheumatoid arthritis. The main question is whether these pharmacological and traditional approaches can produce durable control of inflammatory polarization.
2 papers · 11.1%
Macrophages are not uniformly drivers of tissue injury but can be adaptive effectors of repair
The MASH liver-macrophage study and the mouse full-thickness endometrial-injury regeneration study challenge the set’s prevailing assumption that macrophages are principally inflammatory or tissue-damaging cells. In MASH, infiltrating lipid-associated macrophages are described as an adaptive response that mitigates lipotoxic stress, clears death signals, and supports resolution and fibrosis regression, although chronic exposure can redirect them toward inflammatory and fibrogenic activity 42743990Sep. In endometrial injury, macrophages are indispensable during early regeneration and promote SFRP4-positive stromal-cell reprogramming through TNF-α, thereby enhancing tissue restoration 42234562Jun. The resulting change is a context-dependent account in which macrophages can initiate or enable repair, rather than being treated as intrinsically pathogenic targets for depletion or suppression.
Papers
The 18 papers from the last 6 months that study macrophage directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Macrophage Roles in Tissue Injury (9)
- Context-Dependent Roles of Liver Macrophages in MASH. Seminars in liver disease · 15 Sept 2026 PMID 42743990
- CCL5 mRNA-enriched small extracellular vesicles from renal tubular epithelial cells enhance macrophage inflammatory responses in diabetic nephropathy. Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 5 Sept 2026 PMID 42700225
- pH-Responsive liposomes co-delivering a membrane-active peptide and the PI3Kγ inhibitor to reconstruct the tumor microenvironment for enhanced antitumor immunotherapy. Biomaterials science · 17 Aug 2026 PMID 42605855
- Mannose-modified tobacco mosaic virus-mediated macrophage regulation inhibits pulmonary fibrosis progression. Journal of materials chemistry. B · 3 Aug 2026 PMID 42544440
- Asymmetric hydrogel with "spear-shield" properties promotes diabetic foot ulcer healing by modulating macrophage autophagy. Journal of controlled release : official journal of the Controlled Release Society · 6 Jul 2026 PMID 42409241
- Injectable pH-responsive gelatin methacryloyl hydrogel for cuproptosis-synergized sunitinib therapy and immune reprogramming in clear cell renal cell carcinoma. Acta biomaterialia · 2 Jul 2026 PMID 42392517
- Macrophage-enriched GPR91 aggravates acute liver injury by inhibiting efferocytosis via the AC/cAMP/PPARγ pathway. Metabolism: clinical and experimental · 23 Jun 2026 PMID 42336269
- Macrophage-Mediated In Vivo Intracellular Crystallization of Aluminum Oxyhydroxide Adjuvant in Vaccine-Induced Granulomas. ACS applied materials & interfaces · 30 Apr 2026 PMID 42062044
- Systemic depletion of CD11b+ cells improves metabolic function in murine model of sleep apnea induced by intermittent hypoxia. Sleep · 27 Apr 2026 PMID 42041119
Spatial Mapping of Macrophage States (4)
- Spatial biology reveals altered macrophage states in immunosuppressed non-melanoma skin cancer. Cell · 5 Aug 2026 PMID 42556334
- TAM-targeted nanomedicine in cancer: biological basis, therapeutic strategies, and translational perspectives. Theranostics · 29 Jun 2026 PMID 42370186
- Spatial and temporal single cell multi-omics in mice reveals macrophage-SFRP4+ stroma interactions promoting endometrial regeneration via TNF-α. Cell reports · 3 Jun 2026 PMID 42234562
- Uncovering spatially resolved functional genomics with CRISPR screen sequencing. Cell · 26 May 2026 PMID 42190664
Macrophage Ferroptosis in Disease (3)
- Targeting FAR1 to inhibit intestinal macrophage ferroptosis: repurposing irinotecan as a novel sepsis therapy. Apoptosis : an international journal on programmed cell death · 19 Aug 2026 PMID 42616198
- Emerging biomedical and pharmaceutical strategies for the treatment of atherosclerosis: from conventional lipid-lowering therapy to nanomedicine. Journal of applied biomedicine · 23 Jun 2026 PMID 42333862
- MCL inhibits macrophage ferroptosis through the NRF2/HO-1/GPX4 axis to attenuate carotid atherosclerotic plaque formation. International immunopharmacology · 22 Jun 2026 PMID 42330582
Macrophage Polarization in Inflammation (2)
- Design, synthesis, and evaluation of indole-pyridine chalcone derivatives as novel HK2 inhibitors to modulate macrophage glycolysis and inflammation for IBD treatment. European journal of medicinal chemistry · 11 May 2026 PMID 42114226
- Zhiwang decoction inhibits the inflammatory response and macrophage polarization in rheumatoid arthritis by mediating the PI3K/AKT phosphorylation pathway through cellular communication network factor 1. Journal of ethnopharmacology · 4 May 2026 PMID 42081959
By study type
Preclinical: animal, cell and lab studies (16)
- CCL5 mRNA-enriched small extracellular vesicles from renal tubular epithelial cells enhance macrophage inflammatory responses in diabetic nephropathy. Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 5 Sept 2026 PMID 42700225
- Targeting FAR1 to inhibit intestinal macrophage ferroptosis: repurposing irinotecan as a novel sepsis therapy. Apoptosis : an international journal on programmed cell death · 19 Aug 2026 PMID 42616198
- pH-Responsive liposomes co-delivering a membrane-active peptide and the PI3Kγ inhibitor to reconstruct the tumor microenvironment for enhanced antitumor immunotherapy. Biomaterials science · 17 Aug 2026 PMID 42605855
- Spatial biology reveals altered macrophage states in immunosuppressed non-melanoma skin cancer. Cell · 5 Aug 2026 PMID 42556334
- Mannose-modified tobacco mosaic virus-mediated macrophage regulation inhibits pulmonary fibrosis progression. Journal of materials chemistry. B · 3 Aug 2026 PMID 42544440
- Asymmetric hydrogel with "spear-shield" properties promotes diabetic foot ulcer healing by modulating macrophage autophagy. Journal of controlled release : official journal of the Controlled Release Society · 6 Jul 2026 PMID 42409241
- Injectable pH-responsive gelatin methacryloyl hydrogel for cuproptosis-synergized sunitinib therapy and immune reprogramming in clear cell renal cell carcinoma. Acta biomaterialia · 2 Jul 2026 PMID 42392517
- TAM-targeted nanomedicine in cancer: biological basis, therapeutic strategies, and translational perspectives. Theranostics · 29 Jun 2026 PMID 42370186
- Macrophage-enriched GPR91 aggravates acute liver injury by inhibiting efferocytosis via the AC/cAMP/PPARγ pathway. Metabolism: clinical and experimental · 23 Jun 2026 PMID 42336269
- Emerging biomedical and pharmaceutical strategies for the treatment of atherosclerosis: from conventional lipid-lowering therapy to nanomedicine. Journal of applied biomedicine · 23 Jun 2026 PMID 42333862
- MCL inhibits macrophage ferroptosis through the NRF2/HO-1/GPX4 axis to attenuate carotid atherosclerotic plaque formation. International immunopharmacology · 22 Jun 2026 PMID 42330582
- Uncovering spatially resolved functional genomics with CRISPR screen sequencing. Cell · 26 May 2026 PMID 42190664
- Design, synthesis, and evaluation of indole-pyridine chalcone derivatives as novel HK2 inhibitors to modulate macrophage glycolysis and inflammation for IBD treatment. European journal of medicinal chemistry · 11 May 2026 PMID 42114226
- Zhiwang decoction inhibits the inflammatory response and macrophage polarization in rheumatoid arthritis by mediating the PI3K/AKT phosphorylation pathway through cellular communication network factor 1. Journal of ethnopharmacology · 4 May 2026 PMID 42081959
- Macrophage-Mediated In Vivo Intracellular Crystallization of Aluminum Oxyhydroxide Adjuvant in Vaccine-Induced Granulomas. ACS applied materials & interfaces · 30 Apr 2026 PMID 42062044
- Systemic depletion of CD11b+ cells improves metabolic function in murine model of sleep apnea induced by intermittent hypoxia. Sleep · 27 Apr 2026 PMID 42041119
Unclassified: not yet indexed with MeSH (2)
- Context-Dependent Roles of Liver Macrophages in MASH. Seminars in liver disease · 15 Sept 2026 PMID 42743990
- Spatial and temporal single cell multi-omics in mice reveals macrophage-SFRP4+ stroma interactions promoting endometrial regeneration via TNF-α. Cell reports · 3 Jun 2026 PMID 42234562
Written from 18 PubMed abstracts, each one listed by PMID above. Published: 2026-06-15. Last written: 2026-09-17 by GPT. Corrections: 2026-09-26 by GPT. Drafted by language models from published abstracts; not medical advice.