Signaling

2026 review of M1/M2 polarization: signaling pathways, markers, lab techniques, and current understanding of the spectrum beyond the binary model.

Comprehensive review of macrophage signaling: NF-kB, JAK-STAT, MAPK, and their roles in homeostasis and disease.

M1/M2 is a simplification; macrophages span a spectrum of phenotypes determined by the local microenvironment.

M1/M2 balance drives tissue repair vs chronic inflammation; resolution-based strategies reviewed. IL-10 and TGF-beta as resolution mediators.

2026 review of PRRs: TLRs, CLRs, NLRs, and RLRs: the receptors that tell the macrophage what it has eaten and what to do next.

Metabolic state modulates efferocytosis; M1 metabolic signature (glycolysis-heavy) vs M2 (oxidative phosphorylation) shapes clearance capacity.

Efferocytosis failure as shared signaling defect across autoimmune disease; MERTK, AXL, TIM4 receptor downregulation as common mechanism.

Leishmania subverts macrophage immunometabolism to survive intracellularly; review covers resistance mechanisms and next-generation therapeutics targeting this interface.

Efferocytosis near vascular niches rewires macrophage chromatin accessibility; signals downstream of apoptotic cell uptake drive proangiogenic phenotype.

Large microparticles (~3 um) compete with apoptotic cells and reduce macrophage efferocytic signaling capacity. Particle size is a signaling variable.

Review of efferocytosis signaling disruptions in atherosclerosis and myocardial infarction; impaired apoptotic cell clearance as driver of plaque progression.

Single-cell sequencing identifies efferocytosis gene signatures correlating with immune infiltration and prognosis in PDAC; macrophage clearance capacity predicts tumor behavior.

Enhancing efferocytosis in degenerating discs shifts macrophages toward anti-inflammatory phenotypes (IL-10, TGF-beta); proposed as a strategy to slow disc degeneration. Cell Proliferation 2025.

Diabetic wound microenvironment impairs efferocytosis, which blocks M1-to-M2 transition; the clearance-polarization axis is central to why chronic diabetic wounds fail to resolve. J Inflamm Res 2026.

Efferocytosis is not merely debris clearance; it is a pro-resolving signal in its own right. Macrophage uptake of apoptotic cells triggers downstream anti-inflammatory programming that actively accelerates wound closure. Commun Biol 2026.

Comprehensive 2026 review of the efferocytosis signaling cascade: find-me signals (ATP, LPC), eat-me signals (PtdSer), don't-eat-me signals (CD47), and downstream resolution programs, with therapeutic interventions targeting each node. MedComm 2026.

Comprehensive 2026 review positioning impaired efferocytosis as a shared mechanism across obesity, T2DM, MASLD, and atherosclerosis; metaflammation driven by apoptotic cell accumulation resists conventional anti-inflammatory drugs; efferocytosis restoration proposed as therapeutic lever across metabolic disease.

Mathematical model of M1/M2 polarization as the decision point between sterile inflammation resolving vs progressing to chronicity; integro-differential reaction-diffusion framework tracking 17 mediators including DAMPs, inflammatory cytokines, and tissue-resident macrophages. Computational study.

2026 review of neutrophil efferocytosis in IBD, chronic gastritis, NAFLD/NASH, and pancreatitis; shared defect mechanisms include IL-10R signaling failure, receptor shedding, CD47 upregulation, and SPM deficiency; natural product-based therapeutic strategies covered. Frontiers in Immunology 2026.

TAMs develop spatially and functionally heterogeneous programs shaped by hypoxia, metabolic stress, and chronic IFN-gamma exposure; chronic IFN-gamma can paradoxically promote immune resistance through checkpoint induction and epigenetic remodeling.

Persistent eosinophilia in CRSwNP attributed to MerTK-competent macrophage subset loss and skewed receptor repertoire, not only excess recruitment; cascade-anchored model of efferocytosis failure driven by IL-10-dependent signaling defects; bridges macrophage biology to type 2 airway disease.

2026 review of M1/M2 polarization signaling: TLR4/NF-kB, JAK/STAT, PI3K/Akt, Notch, TGF-beta/Smad; metabolic underpinning (glycolysis for M1, FAO/OXPHOS for M2); therapeutic strategies from small molecules to CAR-M macrophages and epigenetic reprogramming. March 2026.

Review in Journal of Pathology 2026: microglia efferocytosis in Alzheimer's, Parkinson's, stroke, and TBI; proposes immune-metabolism coupling as a unifying mechanism and disease-context-specific therapeutic targets; single-cell sequencing as the analytical frame.

Cell volume disruption interpreted as a danger signal: VRAC (volume-regulated anion channel) loss amplifies TBK1-dependent type I IFN responses; swelling synergizes with pathogen-sensing pathways and exacerbates influenza-induced cytokine storm; J Cell Biol 2026.

Efferocytosis drives tumor macrophage polarization toward M2/immunosuppressive states through multiple signaling pathways; impaired clearance creates an immunosuppressive TME; targeting efferocytosis-M2 crosstalk proposed as cancer therapeutic strategy. Int Immunopharmacol 2026.

SerpinB2 maintains VAT-resident macrophage survival via mitochondrial OXPHOS and antioxidant glutathione; IFN-gamma in obesity activates Ikaros to suppress SerpinB2 expression, depleting resident macrophages and impairing metabolic homeostasis; IFN-gammaR deletion or glutathione supplementation rescues the phenotype. Nat Commun 2026.

Review (Signal Transduct Target Ther 2026) of macrophage signaling combined with synthetic receptor engineering (CAR-M, CD3zeta); covers scalable manufacturing, regulatory compliance, and key pathways (phagocytic receptors, complement, mannose receptor) as therapeutic levers. August 2026.

Chinese review (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2026) of macrophage efferocytosis mechanisms in non-infectious inflammatory diseases; surveys how impaired apoptotic cell clearance drives persistent inflammation across rheumatologic, metabolic, and CNS disease contexts.

Front Immunol 2026 review integrating macrophage polarization biology with methodological landscape (single-cell transcriptomics, spatial transcriptomics, flow cytometry, ex vivo models); maps M1/M2 plasticity concepts to experimental approaches and identifies translational gaps.

Front Immunol 2025: single-cell and spatial transcriptomics in zebrafish wound model resolve macrophage transcriptional states across time; captures early pro-inflammatory to late reparative transition at single-cell resolution and identifies transitional states not captured by binary M1/M2 framing.

MedComm 2026 review: macrophage phenotypic plasticity is intrinsically linked to metabolic reprogramming; covers glycolytic shift in M1, OXPHOS in M2, and metabolic intermediates (succinate, itaconate, alpha-KG) as direct regulators of transcription factor activity and inflammatory gene expression.

Front Immunol 2026: frames macrophages as metabolic hubs that recycle nutrients from engulfed cargo to surrounding tissues; explores how the metabolic nature of phagocytosed material shapes downstream polarization; evolutionary perspective linking professional phagocytosis to tissue nutrient economy.

Inflamm Res 2026: metabolite-sensing receptors (GPCRs and nuclear receptors) detect intracellular intermediates and extracellular metabolites from diet, host tissues, and microbiome; maps how immunometabolic crosstalk through these receptors dictates M1-to-M2 shift and resolution of inflammation.

Front Immunol 2026: early post-injury macrophages shift to glycolysis and pentose phosphate pathway (pro-inflammatory); metabolic reprogramming toward OXPHOS and fatty-acid oxidation drives resolution and repair; bi-directional macrophage-fibroblast crosstalk sustains physiological remodeling but maladapts to fibrosis under persistent inflammation.

Eur J Trauma Emerg Surg 2026: reviews how mechanical and sterile tissue trauma rapidly recruits and reprograms macrophages; distinguishes DAMPs-driven sterile inflammation from pathogen-driven responses; positions macrophage functional state at time of secondary injury as a determinant of repair vs. chronic inflammation.

Immunometabolism 2026: resolvins (DHA-derived specialized pro-resolving mediators) reprogram macrophage metabolism toward OXPHOS and FAO, accelerate efferocytosis, and shift polarization toward reparative phenotype; provides mechanistic link between lipid mediator production and the macrophage metabolic state during resolution.

J Enzyme Inhib Med Chem 2026: ATP-citrate lyase (ACLY) controls intracellular acetyl-CoA production, linking citrate metabolism to histone acetylation and chromatin remodeling; ACLY inhibition shifts macrophages from M1 to resolution phenotype by reducing acetylation of inflammatory gene loci; candidate therapeutic target for chronic inflammation.

Front Immunol 2025: systematic review of phosphorylation, ubiquitination, methylation, acetylation, and lactylation in macrophage polarization; maps signal-responsive and metabolism-sensitive PTM networks that gate M1/M2 switching; identifies druggable nodes across each modification class.

FEBS Open Bio 2026: comparative review of bactericidal mechanisms across neutrophils, macrophages, and Dictyostelium; four conserved phagolysosomal killing systems (ROS/RNS, bactericidal ions, lysosomal enzymes, membrane-permeabilizing peptides) with built-in redundancy; evolutionary conservation from amoeba to mammal supports ancient origin of professional phagocytosis.

IUBMB Life 2026: combined scRNA-seq, spatial transcriptomics, and in vitro validation resolve macrophage subpopulation diversity and niche localisation in carotid plaques; identifies regulatory mechanisms specific to plaque microenvironments and candidate therapeutic targets in atherosclerosis.

Front Immunol 2026: comprehensive atlas of plaque macrophage states (inflammatory, interferon-responsive, lipid-associated, foamy, resident-like, reparative) each mapped to distinct microanatomic niches and multicellular communication networks; redefines plaque macrophage heterogeneity beyond M1/M2.

J Transl Med 2026: spatial and single-cell analysis of colorectal cancer liver metastases identifies mCAF-SPP1+ macrophage-T cell axis as architect of immunosuppressive niches; crosstalk between cancer-associated fibroblasts, SPP1-expressing macrophages, and exhausted T cells creates a spatially organised barrier to immune clearance.

Signal Transduct Target Ther 2026: comprehensive review of fibrosis mechanisms across lung, liver, heart, and kidney; macrophage-to-myofibroblast crosstalk, TGF-beta signaling, and macrophage polarization toward profibrotic states as shared drivers; emerging therapeutic strategies including RNA therapy and macrophage reprogramming reviewed.

Mucosal Immunol 2026: tissue-resident macrophages in colon survive acute DSS colitis and contribute to repair phase; distinct from infiltrating monocyte-derived macrophages that dominate during peak inflammation; demonstrates functional adaptation of the resident pool rather than replacement.

Cell Rep 2025: different commensal bacteria drive distinct macrophage transcriptional and functional states; Fusobacterium nucleatum drives inflammatory responses while Mediterraneibacter gnavus tempers them; demonstrates microbiome composition as a determinant of mucosal macrophage phenotype.

Cell Syst 2026: primary data showing human macrophages trained with different stimuli encode distinct stimulus-specific memory patterns; restimulation responses strongest to stimuli similar to initial training; differential licensing of inflammatory transcription factors correlates with specificity encoded in chromatin at day 6 post-training.

Cells 2026: review of epigenetic reprogramming (H3K4me3, H3K27ac accumulation) and metabolic rewiring (mTOR-HIF-1alpha, aerobic glycolysis, succinate) as mechanisms of trained immunity across neutrophils, monocytes, and macrophages; pathophysiological roles in infection, autoimmunity, and chronic inflammation.

Front Immunol 2026: gout monosodium urate crystals induce trained immunity in macrophages via epigenetic marks and metabolic reprogramming; trained macrophages exhibit exaggerated responses to secondary stimuli, contributing to the episodic flares of crystal arthritis; proposes trained immunity as a mechanism of gout chronicity.

Atherosclerosis 2026: lactate drives macrophage foam cell formation via histone lactylation (H3K18la) at cholesterol efflux gene promoters (ABCA1, ABCG1, SR-B1), suppressing efflux and promoting lipid retention; Mg2+ supplementation attenuates this effect; mechanistic link between metabolic microenvironment and plaque progression.

Aging Dis 2026: senescent macrophages accumulate with age and in chronic disease; SASP drives tissue inflammation while impaired phagocytosis compromises clearance; context-dependent outcomes include facilitating tissue remodeling vs. fueling inflammaging; senolytic targeting proposed as therapeutic strategy for age-associated conditions and MASLD.

Adv Immunol 2026: brain macrophages (microglia, perivascular macrophages, border-associated macrophages) are anatomically specialised populations rather than uniform responders; niche, developmental origin, and regulatory state determine functional outcome in neurodegeneration; reviews heterogeneity beyond DAM/homeostatic binary and therapeutic implications.

J Immunol 2026: LPS-activated macrophages resist ferroptosis via GCH1-BH4 pathway; LPS+IFN-gamma-activated macrophages switch to iNOS-derived nitric oxide for ferroptosis resistance; defines a polarisation-state-dependent axis (GCH1-BH4-iNOS) governing macrophage cell death susceptibility during inflammatory activation.

Chin Med J (Engl) 2026: ferroptosis induction reshapes macrophage glucose metabolism; iron-dependent lipid peroxidation feeds back onto glycolytic and pentose phosphate pathway activity; positions ferroptosis as a metabolic regulator rather than simply a cell death endpoint in macrophage biology.

Neuron 2026: lineage tracing, pharmacological microglia depletion, and multi-omics profiling reveal that monocyte-derived macrophages from blood and skull bone marrow engraft in brain parenchyma and display transcriptional and epigenetic landscapes distinct from yolk-sac-derived microglia; establishes ontogeny as a determinant of brain macrophage identity beyond tissue environment.

Front Immunol 2025: maps developmental origins of synovial macrophages (lining and sublining compartments) across embryonic and postnatal stages; identifies yolk-sac-derived and monocyte-derived contributions to steady-state and inflammatory synovium; relevant to rheumatoid arthritis macrophage targeting.

J Transl Med 2026: mitophagy maintains mitochondrial fitness to suppress inflammation and support OXPHOS in the reparative macrophage phenotype after MI; M1-to-M2 switch driven by mitochondrial metabolic reprogramming regulated by autophagy; review with therapeutic implications for cardiac repair.

Int Immunopharmacol 2026: macrophage autophagy dynamically balances immune responses in allergic disease by eliminating damaged organelles and regulating mTOR and NF-kappaB signaling; autophagy dysfunction linked to asthma, atopic dermatitis, and allergic rhinitis; reviews crosstalk with Th2 immunity and candidate therapeutic targets.

Front Immunol 2026: complement receptor-mediated engulfment (ADCP) operates as a distinct pathway from FcgR-mediated phagocytosis in monoclonal antibody cytotoxicity; complement pathway can bypass FcgR-associated hypophagia; combined FcgR + complement engagement is additive for target removal, with implications for antibody engineering and macrophage-mediated cancer immunotherapy.

Metabolism 2026: adipose tissue macrophages link obesity-driven chronic inflammation to ECM remodeling and fibrosis; ATMs cannot be adequately described by M1/M2 dichotomy (single-cell and spatial omics reveal greater heterogeneity); profibrotic ATM subsets identified as mediators of adipose dysfunction and systemic metabolic disease.

Int J Mol Sci 2026: ATMs retain an inflammatory memory detectable as a CD68+ macrophage footprint that persists through weight loss and re-expansion cycles; trained immunity mechanism links repeated adipose inflammation to escalating cardiometabolic risk and cancer susceptibility during weight cycling.

Cytokine 2026: single-cell RNA-seq and multi-omics redefine ATM heterogeneity beyond M1/M2; identifies distinct ATM subpopulations associated with metabolic inflammation, lipid handling, and tissue repair; maps ATM states to disease progression in obesity, MASH, and type 2 diabetes.

Front Immunol 2026: exosomes from diverse cell types carry proteins, nucleic acids, and lipids that reprogram macrophage polarization, phagocytic capacity, and inflammatory output; CD4+ T cell EVs bearing surface IFN-gamma activate STING in recipient macrophages; cancer-cell-derived exosomes metabolically reprogram TAMs; positions exosomes as bidirectional regulators of macrophage function.

Int J Mol Sci 2026: single-cell and spatial omics reveal marked state heterogeneity among synovial macrophages in RA beyond M1/M2; M1-like macrophages drive synovial inflammation and pannus via TNF-alpha/IL-1beta/IL-6; novel subsets including SPP1+ and resident-like synovial lining macrophages identified as disease-relevant; cytokine network mapping for therapeutic target prioritisation.

Cells 2026: synovial macrophage metabolic reprogramming (glycolytic shift, citrate accumulation, itaconate/succinate imbalance) sustains pathogenic inflammatory states and impairs resolution in RA; maps metabolic vulnerabilities as therapeutic targets; reviews implications for JAK inhibitors and emerging immunometabolic interventions.

Gut Microbes 2026: probiotic-derived vesicles reprogram macrophage metabolic state through glycolytic and oxidative pathways; microbiota-immune communication shapes macrophage polarization with implications for chronic inflammation, metabolic disorders, and inflammatory bowel disease.

Biochem Pharmacol 2026: single-cell RNA-seq identifies dysregulated Fgr kinase as a driver of macrophage imbalance; apigenin inhibits Fgr, promotes IL-10 secretion, and restores immune-vascular homeostasis in a mouse model; demonstrates pharmacological targeting of macrophage signaling at the reproductive-immune interface.

Circulation 2026: TET2 clonal hematopoiesis impairs macrophage glycolysis, which in turn blocks efferocytosis and prevents plaque resolution; lactate supplementation or HIF-1alpha activation with molidustat rescues efferocytic capacity and promotes plaque restructuring in mice; glycolysis-efferocytosis axis as a therapeutic lever in clonal hematopoiesis-driven atherosclerosis.

Metabolism 2026: GPR91 (succinate receptor) in macrophages suppresses efferocytosis through the adenylyl cyclase/cAMP/PPARgamma axis; GPR91 deficiency enhances dead-cell clearance and attenuates CCl4-induced hepatic inflammation; positions GPR91 as a metabolite-sensing brake on efferocytic resolution.

Ageing Res Rev 2026: macrophage senescence and cell death (apoptosis, pyroptosis, ferroptosis, efferocytosis failure) act in concert to sustain chronic plaque inflammation; senolytics, NLRP3 inhibitors, ferroptosis suppressors, and autophagy enhancers reviewed as candidate strategies; maps cross-talk between senescence and death pathways as a unified therapeutic target.

Sci Adv 2026: BCG plus bacterial lipoprotein co-immunization expands CCR5hi memory-like monocytes that provide long-term protection against polymicrobial sepsis; lactate drives histone H3K18 lactylation to open antimicrobial gene loci; metabolic-epigenetic axis (lactate-lactylation) as a durable innate immune memory mechanism.

mBio 2026: Mtb-infected macrophages prime neighboring uninfected bystanders through IL-1beta/NF-kB signaling, conferring enhanced antimicrobial capacity; intercellular propagation of trained immunity expands the protective response population-wide during infection without direct bacterial contact.

Front Cell Infect Microbiol 2026: M. fortuitum-trained caprine alveolar macrophages show elevated TNF-alpha and IL-1beta production and enhanced phagosomal acidification upon re-stimulation; trained immunity can be induced in lung macrophages, with implications for mucosal vaccine strategies against pulmonary mycobacterial infections.

Gut Microbes 2026: dietary fiber enriches propionate-producing gut bacteria; propionate metabolically reprograms alveolar macrophages and attenuates sterile lung inflammation while modulating infectious injury responses; gut-lung immunometabolic axis mediated through SCFA-driven macrophage reprogramming.

Int Immunopharmacol 2026: CD301b+ tissue-resident macrophage subpopulation identified as an early-responder orchestrating pro-repair and osteogenic states after injury; depletion impairs bone healing and reduces osteogenic factor expression; defines a specific tissue-resident subset as a functional driver of repair rather than a generic macrophage response.

JHEP Rep 2026: ethanol suppresses macrophage efferocytosis of apoptotic hepatocytes by disrupting the PI3K/AKT/SREBP1-FASN-NRF2-TREM2 lipogenesis axis; FASN-dependent lipid synthesis is required for efferocytic capacity in liver macrophages; impaired clearance sustains hepatocyte death and chronic liver inflammation in ALD.

J Lipid Res 2026: MDA-epitopes on dying cell surfaces act as oxidative damage markers that activate complement proteins and regulate opsonization for phagocytic clearance; connects lipid peroxidation on apoptotic cells to immune recognition and modulation of efferocytosis efficiency.

Clin Invest Med 2026: Dicer1 loss in macrophages impairs efferocytosis and delays wound repair; increased pentose phosphate pathway activity in Dicer1-deficient macrophages sustains a pro-inflammatory metabolic state; miRNA processing by Dicer1 required for macrophage metabolic-efferocytic transition during wound resolution.

Autophagy 2026: fluorescent biosensor mouse reveals cell-type-specific lipid droplet degradation patterns in atherosclerotic plaques; TREM2+ macrophage foam cells show reduced lipophagy relative to smooth muscle foam cells; lipophagy-immunometabolism interplay as a distinguishing feature of macrophage versus non-macrophage foam cell biology.

Protein Cell 2026: review of how complement opsonization directs phagocytic clearance of apoptotic cells, pathogens, and cellular debris; receptor-ligand pairs (CR3, CR4, C1q receptors) and their downstream signaling during complement-mediated efferocytosis and pathogen phagocytosis; positions complement as a bridge between innate sensing and phagocyte execution.

J Clin Invest 2026: efferocytosis triggers base excision repair of oxidized DNA in macrophages via DNMT3A activation; this epigenetic-repair axis enables macrophage proliferation required for tissue resolution; loss of DNMT3A (as in clonal hematopoiesis) impairs this pathway and prevents resolution in atherosclerosis regression models.

J Leukoc Biol 2026: loss of H3K4 methyltransferases Kmt2c or Kmt2d impairs macrophage pro-inflammatory cytokine output and phagocytic capacity; H3K4 methylation-dependent chromatin accessibility shapes both inflammatory gene expression and innate metabolic function; positions KMT2C/D as epigenetic gatekeepers of macrophage identity.

Antioxid Redox Signal 2026: urokinase plasminogen activator receptor (uPAR) amplifies macrophage NF-kB-driven inflammatory signaling to promote fibrotic tissue remodeling; uPAR as a surface receptor that integrates pro-inflammatory signals in macrophages and drives chronic fibrosis-associated inflammation.

Am J Respir Cell Mol Biol 2026: IFN-gamma signaling is uncoupled from iNOS induction in primate myeloid cells; respiratory epithelial cells rather than macrophages are the dominant nitric oxide source in human TB; directly contradicts the mouse-derived assumption that macrophage iNOS/NO is the primary IFN-gamma effector mechanism in human mycobacterial infection.

BBA Mol Basis Dis 2026: prior obesity accelerates MASH progression during weight regain through a macrophage/IGFBP7/hepatic stellate cell axis; IGFBP7 produced by macrophages with prior obesity exposure amplifies HSC activation and fibrosis; obesity history leaves a macrophage-mediated fibrotic memory independent of current body weight.

Mol Immunol 2026: vaping produces sex-specific pulmonary macrophage reprogramming; male mice show inflammatory polarization and suppressed immune-response genes, while females show preserved homeostatic identity with altered lipid synthesis; sex is a biological variable in macrophage responses to inhaled xenobiotics that standard analysis misses.

Biochem Biophys Res Commun 2026: preclinical systematic review identifies 35 endogenous factors regulating efferocytosis in atherosclerosis; metabolic regulators PKM2 and PFKFB3 are central; metabolic reprogramming supports efficient apoptotic cell clearance and inflammation resolution; maps the regulatory landscape for therapeutic target selection.

Biomed Pharmacother 2026: Netrin-1 and Semaphorin-3E act as macrophage retention factors perpetuating plaque inflammation; CCR7-mediated egress promotes macrophage emigration and resolution; effective efferocytosis is essential for tissue homeostasis and its dysregulation drives disease progression; reviews molecular levers for therapeutic plaque regression.

Ann Med 2026: exosome-delivered METTL3 installs m6A modifications that drive miR-155-5p maturation and M1 macrophage polarization; downstream activation of NLRP3/TLR4/caspase-1 amplifies inflammatory output; positions epitranscriptomic transfer between cells as an intercellular mechanism for macrophage activation state propagation.

Front Biosci 2026: dexmedetomidine activates Nrf2/HO-1 to suppress macrophage ferroptosis and reduce oxidative stress in sepsis-associated lung injury; Nrf2-dependent mechanism attenuates pro-inflammatory macrophage polarization; positions the Nrf2/HO-1 axis as a pharmacological brake on macrophage ferroptotic death in acute inflammatory contexts.

Front Immunol 2026: single-cell analysis of SCI myeloid populations identifies an HMOX1-high subpopulation that concentrates ferroptosis-related molecular changes and progresses toward inflammation-amplifying states; HMOX1 links disturbed iron handling, ferroptosis, and myeloid inflammatory remodeling as a candidate hub gene.

Vet Immunol Immunopathol 2026: review applies an evidence-to-claim framework to macrophage phenotype and MAP persistence in Johne's disease; finds support for disease-stage-associated differences in macrophage responsiveness but identifies gaps in tissue-specific macrophage state data during natural infection; macrophage activation state as the decisive variable in mycobacterial persistence.

Free Radic Biol Med 2026: indium-tin oxide nanoparticle exposure drives foam macrophage accumulation and lipid metabolism disorder in rat lung; alveolar macrophages are the primary mediators of progressive fibrosis; identifies oxidative-stress-driven macrophage lipid dysregulation as the mechanism linking particle exposure to fibrotic lung disease.

Hepatol Commun 2026: FGF21-overexpressing MSCs enhance macrophage phagocytic capacity in APAP-induced acute liver injury, accelerating dead-cell clearance and tissue repair; demonstrates a paracrine circuit in which a secreted metabolic hormone boosts macrophage efferocytic function in an acute sterile injury setting.

Arterioscler Thromb Vasc Biol 2026: EGLN3 suppresses NLRP3 inflammasome assembly and modulates foam cell formation and efferocytosis in atherosclerotic macrophages through a mechanism independent of its prolyl hydroxylase activity; separates oxygen-sensing catalysis from anti-inflammatory macrophage signaling in plaque biology.

Arterioscler Thromb Vasc Biol 2026: PIM1 kinase in macrophages upregulates CD36 scavenger receptor through PPARgamma signaling, enhancing lipid uptake and foam cell formation; PIM1/PPARgamma/CD36 axis as a targetable pathway for modulating macrophage lipid metabolism and reducing atherosclerotic plaque progression.

Acta Biomater 2026: mechanically adaptive hydrogels restore macrophage-mediated efferocytosis by suppressing Piezo1-YAP mechanotransduction; macrophage phagocytic rate of apoptotic cells rises from 22.5% to 64.5%; mechanosensing as a regulator of macrophage clearance capacity and downstream fibrotic outcome.

Biochem Biophys Rep 2026: cardiomyocyte-derived exosomal NEAT1 accumulates in infiltrating macrophages and blocks IRG1-itaconate production, driving pro-inflammatory polarization post-MI; intercellular lncRNA transfer as a mechanism by which damaged tissue reprograms macrophage immunometabolism toward inflammation.

Biomed Pharmacother 2026: review of KDM6B (JMJD3), an H3K27me3 demethylase that governs macrophage polarization and metabolism across tumor, inflammatory, and fibrotic contexts; KDM6B-mediated macrophage regulation is microenvironment-dependent; positions KDM6B as a context-sensitive epigenetic hub for macrophage state control.

Transl Res 2026: review of how DNA methylation, histone modifications, and non-coding RNAs direct macrophage polarization during asthmatic airway inflammation; epigenetic mechanisms form a regulatory network bridging environmental exposures to macrophage activation state; identifies targets for intervention in airway inflammatory disease.

Phytomedicine 2026: senescent macrophages in RA accumulate lactate-driven H3K18 lactylation via SMAD4-MCT1 signaling; paederoside blocks this axis and shifts macrophages from M1 to M2 polarization; macrophage senescence and lactylation as pharmacologically tractable nodes in chronic inflammatory joint disease.

J Immunother Cancer 2026: RAB31 stabilizes FPR2 receptor via clathrin-mediated endocytosis in tumor-associated macrophages, enabling ANXA1-driven immunosuppressive education; RAB31 deficiency reprograms TAMs to M1-like phenotype and enhances CD8+ T cell infiltration; endosomal trafficking as a checkpoint of macrophage immunosuppressive state.

Neoplasia 2026: NSUN2-dependent m5C RNA methylation in tumor cells prevents macrophage M1 polarization and infiltration, enabling EGFR-TKI resistance; NSUN2 suppression converts immunologically cold tumors to hot by reprogramming macrophage recruitment and activation state; epitranscriptomic tumor-macrophage crosstalk as a resistance mechanism.

eLife 2026: complement C3 enhances trained immune responses in alveolar macrophages through C3aR signaling, boosting glycolytic activity and inflammatory cytokine production on secondary stimulation; C3-deficient macrophages show impaired phagocytosis and reduced ROS generation; positions complement as a modulator of macrophage innate memory formation.

Pharmacol Res 2026: dioscin reprograms macrophages via AMPK activation, suppressing M1 polarization and IL-1beta production; macrophage depletion abolishes the protective effect; AMPK-driven macrophage metabolic reprogramming as the required intermediary between a plant compound and intestinal stem cell recovery.

Med Oncol 2026: oxidized LDL receptor 1 activates NF-kB in tumor-associated macrophages and shifts them toward immunosuppressive M2 polarization, supporting cancer cell proliferation and migration; OLR1/NF-kB as a macrophage-intrinsic axis linking lipid sensing to immunosuppressive state in the tumor microenvironment.

J Mol Histol 2026: adverse lipid conditions increase CD36 while suppressing ABCA1 in macrophages, driving foam cell formation and atherosclerotic inflammation; HDL rescue restores macrophage cholesterol efflux; CD36/ABCA1 balance as the macrophage lipid-handling checkpoint in diabetic atherosclerosis.

Tissue Barriers 2026: review positions cathepsin D, a lysosomal aspartyl protease, as a key regulator of macrophage phenotype and matrix remodeling during tissue repair; its activity shapes inflammatory macrophage responses and ECM degradation essential for barrier recovery in chronic wound contexts.

Bioorg Chem 2026: review of fatty acid-binding proteins in macrophage polarization and tumor immune crosstalk; FABP expression in macrophages is regulated by polarization signals and in turn controls lipid-metabolic state; bidirectional FABP-mediated lipid crosstalk between tumor cells and macrophages as a driver of immune dysfunction and therapeutic resistance.

ACS Appl Mater Interfaces 2026: activated platelet exosomes deliver miR-142-3p to lung macrophages, suppressing M1 polarization and PANoptosis through MAPK pathway inhibition in acute lung injury; platelet-to-macrophage exosomal miRNA transfer as a physiological mechanism for dampening macrophage-driven pulmonary inflammation.

Biochem Biophys Res Commun 2026: dermal stem cells drive macrophages toward CD206+/CD163+ anti-inflammatory phenotype via IL-4 signaling amplifying IL-1Ra production; stromal-immune crosstalk through IL-4Ra-STAT6 as a conserved macrophage immunoregulatory mechanism in tissue repair contexts.

mBio 2026: SKI-II binds VCP and activates the Nrf2 antioxidant pathway in macrophages, promoting M1 polarization and reducing pathogenic ROS to enhance host defense against S. aureus; Nrf2 activation as a macrophage-intrinsic mechanism that simultaneously boosts antimicrobial capacity and controls oxidative collateral damage.

BBA Rev Cancer 2026: review of how TAMs sense metabolic stress and deploy epigenetic reprogramming to sustain immunosuppressive states that resist checkpoint blockade; positions myeloid metabolic-epigenetic plasticity as the central mechanism of TAM immunosuppression and a target for overcoming checkpoint resistance.

Cardiovasc Drugs Ther 2026: review of glycometabolic reprogramming in macrophages as a driver of atherosclerotic plaque development through inflammatory activation; metabolic interventions targeting myeloid glycolysis and oxidative phosphorylation as emerging therapeutic approaches in atherosclerosis.

Circulation 2026: a CD34+ bone-marrow-derived foam-like macrophage population accumulates in transplant arteriosclerosis through collagen-driven CD44-SLC7A11 signaling that increases cystine uptake; blocking this axis reduces macrophage accumulation and inflammatory progression; identifies a macrophage origin and metabolic entry point specific to allograft vascular disease.

JCI Insight 2026: pericardial macrophages are the primary driver of antifibrotic pericardial actions after MI, acting through cystatin C release; macrophage-derived cystatin C suppresses cardiac fibroblast activation and post-infarction remodeling; positions a resident serosal macrophage population as a cardioprotective cellular compartment.

JCI Insight 2026: TY1 noncoding RNA suppresses DNA damage and inhibits cGAS/STING signaling in SSc macrophages, reversing fibrotic markers in mouse models and human cells; cGAS/STING activation in macrophages as an upstream driver of systemic sclerosis fibrosis and a target for nucleic-acid-based intervention.

Mol Biol Rep 2026: algal extract from Egregia menziesii safely modulates LPS-activated macrophage behavior and reduces IL-1beta and IL-6 secretion; adds marine-derived phytochemical candidates to the list of compounds with direct macrophage immunomodulatory activity.

Phytother Res 2026: schisandrin C induces ferroptosis in colorectal cancer cells via PPARgamma and concurrently drives M1 macrophage polarization with increased intratumoral CD86+ infiltration; dual-mechanism plant compound engaging both ferroptotic tumor killing and macrophage reprogramming in the tumor microenvironment.

Stroke 2026: microglia/macrophage-specific SIK3 knockout upregulates CD11c and enhances myelin debris phagocytosis by 19% via C1q-complement axis after ischemic stroke; kinase control of a selective phagocytic receptor as a mechanism for calibrating debris clearance without indiscriminate phagocytosis.

Cancer Immunol Res 2026: LILRA3 functions as a multi-checkpoint antagonist suppressing immunosuppressive myeloid populations; inhibits M2 macrophage polarization and enhances pro-inflammatory cytokine production; positions a leukocyte immunoglobulin-like receptor as a natural brake on macrophage immunosuppressive state in the tumor microenvironment.

Exp Mol Med 2026: FAP-expressing stromal pericyte-like cells in glioblastoma recruit monocytes and drive their conversion into immunosuppressive TAMs through cytokine signaling; identifies a stromal niche cell as an orchestrator of monocyte-to-macrophage differentiation and immunosuppressive programming in brain tumors.

Nature 2026: cancer cells expressing PAI1/PAI2 serpins create fibrin-rich niches that spatially retain macrophages and program them toward immunosuppressive states; blocking serpin activity enhances immunotherapy efficacy; positions a coagulation-pathway molecule as a spatial organizer of macrophage immunosuppression in pancreatic cancer.

BBA Mol Basis Dis 2026: bone marrow MSC-derived exosomes deliver METTL16, which installs m6A modifications via IGF2BP2 to drive GPX1 expression and M2 macrophage polarization in AML; epitranscriptomic crosstalk between stroma-derived exosomes and macrophages as a mechanism of immune suppression in the leukemic niche.

Cell Rep 2026: soluble biofilm factors from S. aureus drive phospho-C/EBPbeta nuclear translocation, suppressing MERTK while leaving MARCO intact; the resulting macrophage subset senses but cannot engulf apoptotic cells; spatial transcriptomics places this subset in biofilm-adjacent wound zones, identifying a mechanism of chronic wound non-resolution.

Small 2026: bifunctional carbon dots restore autophagic flux in mesenchymal stem cells, and MSC-secreted factors in turn enhance macrophage efferocytosis of apoptotic debris in the diabetic bone defect microenvironment; reciprocal MSC-macrophage signaling as a coupled target for bone repair.

Cell Host Microbe 2026: prolonged type I IFN production in Mtb-infected macrophages suppresses their IFNgamma responsiveness; RESIST deletion restores IFNgamma sensitivity and reverses TB susceptibility; positions sustained autocrine type I IFN as a macrophage-intrinsic mechanism of evasion in TB.

PLoS Pathog 2026: in mice, chromatin accessibility profiling after HSV-1 latent infection identifies M1 macrophages (not M2) as the cells acquiring epigenetic memory; trained M1 macrophages mount augmented inflammatory responses on secondary viral challenge; establishes macrophage polarization state as a determinant of trained immunity capacity.

BBA Gen Subj 2026: glioma-derived signals upregulate B3GNT5 in TAMs, driving lacto/neolacto-series glycosphingolipid remodeling that promotes M2-like differentiation; B3GNT5-high TAMs localize to late-differentiation niches in spatial transcriptomics; silencing B3GNT5 reduces macrophage-supported glioma proliferation and invasion; glycosylation as an underexplored layer of TAM programming.

Pharmacol Ther 2026: hepatic crown-like structures (macrophage aggregates encircling dead hepatocytes) sustain chronic liver inflammation in MASH through impaired dead cell clearance; targeting macrophage lysosomal stress with a supramolecular beta-cyclodextrin polyrotaxane resolves CLS formation and reduces fibrosis; positions hepatocyte efferocytosis failure as a druggable driver of MASH progression.

Am J Physiol Lung 2026: review placing alveolar macrophages as central coordinators of AT2-to-AT1 differentiation and scar prevention in the injured lung; phagocytic clearance of dead epithelial cells is the permissive step that unlocks productive repair; macrophage-AT2 crosstalk as a coupled target for fibrosis prevention.

Stroke 2026: in mice, microglial/macrophage SIK3 knockout drives an anti-inflammatory subset that enhances myelin debris uptake via the CD11c-complement axis; white matter preserved after ischemic stroke; SIK3 as a kinase target for promoting reparative phagocytosis.

Sci Immunol 2026: alveolar epithelial cell-targeting manganese-STING agonist liposomes restore lung immune function in aged mice; reversal of age-associated alveolar macrophage senescence restores T cell and B cell responses; heterosubtypic influenza protection achieved in old mice, which conventional vaccines cannot do.

Exp Mol Med 2026: in GBM, FAP-positive pericyte-like stromal cells instruct monocyte differentiation toward immunosuppressive tumor-associated macrophages; FAP-high stroma correlates with TAM abundance and poor prognosis; targeting FAP-mediated monocyte conversion as a route to suppressing the immunosuppressive TME.

Int Immunopharmacol 2026: in mice with acute exacerbation of COPD, resveratrol activates the Nrf2-ferroportin axis in lung macrophages, reducing iron accumulation and lipid peroxidation that drive ferroptosis; positions macrophage ferroptosis as a mechanism of impaired pulmonary immune defense in COPD and Nrf2-FPN as its pharmacological lever.

J Drug Target 2026: plant-derived nanovesicles from Rosa damascena restore efferocytosis in LPS-inflamed macrophages via the GAS6/TAM receptor pathway; GAS6-driven efferocytic balance as a druggable node in the resolution of acute inflammation.

Redox Biol 2026: in human Crohn's disease tissue and mouse models, macrophage-derived selenoprotein P (SELENOP) acts as a redox checkpoint in macrophage-neutrophil crosstalk; SELENOP deficiency amplifies oxidative injury and neutrophil accumulation; positions macrophage-to-neutrophil redox signaling as a driver of intestinal inflammation.

Immunol Invest 2026: single-cell transcriptomics shows beta-elemene skews TAMs from immunosuppressive M2 to antitumor M1 by downregulating CCL2 and blocking Akt/beta-catenin signaling; macrophage reprogramming as the mechanism by which a natural compound suppresses osteosarcoma cancer stem cell maintenance.

Redox Biol 2026: cancer-associated fibroblast-secreted periostin (POSTN) activates integrin beta1 on macrophages, triggering PI3K/AKT/mTOR signaling and driving polarization toward a lipid-stressed immunosuppressive M2 state; fibroblast-to-macrophage metabolic crosstalk as a gastric cancer immune evasion mechanism.

J Mol Cell Cardiol Plus 2026: Netrin-1 selectively inhibits chemokine-driven macrophage migration; systemic Netrin-1 administration prevented aortic sinus enlargement in hyperlipidemic mice; positions axon-guidance cue Netrin-1 as a macrophage-targeted anti-inflammatory approach in vascular disease.

Cell Death Dis 2026: omental macrophages with a mixed M1+/M2+ phenotype secrete IL-1alpha, driving mesothelial cells to undergo mesenchymal transition and enabling peritoneal invasion; a pro-inflammatory macrophage subset as an active structural remodeler at the metastatic front, not merely a bystander.

Immun Ageing 2026: TLR2 activation drives macrophage infiltration and collagen deposition in aging pancreatic islets; TLR2 inhibition reduces insulitis and fibrosis; age-associated sterile inflammation in islets as a macrophage-TLR2 process with implications for type 2 diabetes progression.

J Cell Biol 2026: loss of intramembrane protease Rhbdl2 increases macrophage recruitment speed and accumulation at wound sites through elevated Rac2 protein; identifies a protease-substrate axis controlling the rate at which macrophages populate an injury, not just whether they arrive.

Basic Res Cardiol 2026: obese mice show elevated splenic myelopoiesis and higher myocardial pro-inflammatory macrophage infiltration after infarction; TREM1 is upregulated on these macrophages and its blockade preserves systolic function; TREM1 as the link between metabolic state and adverse cardiac macrophage activation.

Transl Cancer Res 2026: gut dysbiosis-associated Akkermansia depletion accompanies apatinib resistance through reduced M1-like and increased M2-like macrophage fractions; oral Akkermansia repletion restores antitumor macrophage polarization via NF-kB reactivation; microbiome-macrophage axis as a modifiable resistance mechanism.

J Virol 2026: macrophage C-type lectin receptor Mincle (CLEC4E) recognizes lipids and glycolipids in the HCMV envelope and activates proinflammatory signaling; extends Mincle pattern recognition beyond mycobacterial cord factor to a major herpesvirus.