Macrophage plasticity: signaling pathways, tissue repair, and regeneration

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: Aug. 1, 2024

Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.

Language: Английский

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Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 7, 2024

Abstract Tumor-associated macrophages (TAMs) are a heterogeneous population that play diverse functions in tumors. Their identity is determined not only by intrinsic factors, such as origins and transcription but also external signals from the tumor microenvironment (TME), inflammatory metabolic reprogramming. Metabolic reprogramming has rendered TAM to exhibit spectrum of activities ranging pro-tumorigenic anti-tumorigenic, closely associated with progression clinical prognosis. This review implicates diversity phenotypes functions, how this heterogeneity been re-evaluated advent single-cell technologies, impact TME on TAMs. We current therapies targeting metabolism offer new insights for TAM-dependent anti-tumor immunotherapy focusing critical role different programs

Language: Английский

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Unraveling the potential of 3D bioprinted immunomodulatory materials for regulating macrophage polarization: State-of-the-art in bone and associated tissue regeneration

Bioactive Materials, Journal Year: 2023, Volume and Issue: 28, P. 284 - 310

Published: June 1, 2023

Macrophage-assisted immunomodulation is an alternative strategy in tissue engineering, wherein the interplay between pro-inflammatory and anti-inflammatory macrophage cells body determines fate of healing or inflammation. Although several reports have demonstrated that regeneration depends on spatial temporal regulation biophysical biochemical microenvironment biomaterial, underlying molecular mechanism behind still under consideration for developing immunomodulatory scaffolds. Currently, most fabricated platforms reported literature show regenerative capabilities a particular tissue, example, endogenous (e.g., bone, muscle, heart, kidney, lungs) exogenous skin eye). In this review, we briefly introduced necessity 3D scaffolds nanomaterials, focusing material properties their interaction with macrophages general readers. This review also provides comprehensive summary origin taxonomy, diverse functions, various signal transduction pathways during biomaterial-macrophage interaction, which particularly helpful scientists clinicians next-generation From clinical standpoint, discussed role biomaterial and/or nanomaterial composites macrophage-assisted engineering special focus bone associated tissues. Finally, expert opinion presented to address challenges future bioprinted materials engineering.

Language: Английский

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Two new clades recovered at high temperatures provide novel phylogenetic and genomic insights into Candidatus Accumulibacter

ISME Communications, Journal Year: 2024, Volume and Issue: 4(1)

Published: Jan. 1, 2024

Abstract Candidatus Accumulibacter, a key genus of polyphosphate-accumulating organisms, plays roles in lab- and full-scale enhanced biological phosphorus removal (EBPR) systems. A total 10 high-quality Ca. Accumulibacter genomes were recovered from EBPR systems operated at high temperatures, providing significantly updated phylogenetic genomic insights into the lineage. Among these genomes, clade IIF members SCELSE-3, SCELSE-4, SCELSE-6 represent to-date known encoding complete denitrification pathway, suggesting that alone could achieve denitrification. Clade IIC SSA1, SCUT-1, SCELCE-2, SCELSE-8 lack entire set denitrifying genes, representing non-denitrifying Accumulibacter. pan-genomic analysis with other suggested all likely has potential to use dicarboxylic amino acids. aalborgensis AALB affinis BAT3C720 seemed be only two capable using glucose for EBPR. heat shock protein Hsp20 gene was found exclusively which absent clades IA, IC, IG, IIA, IIB, IID, IIG, II-I members. High transcription this SCUT-2 SCUT-3 its role surviving temperatures Ambiguous identity observed newly (SCELSE-9 SCELSE-10). Five machine learning models developed orthogroups as input features. Prediction results they belong new (IIK). The phylogeny re-evaluated based on laterally derived polyphosphokinase 2 gene, showing improved resolution differentiating different clades.

Language: Английский

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Prediction of six macrophage phenotypes and their IL-10 content based on single-cell morphology using artificial intelligence

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Introduction The last decade has led to rapid developments and increased usage of computational tools at the single-cell level. However, our knowledge remains limited in how extracellular cues alter quantitative macrophage morphology such morphological changes can be used predict phenotype as well cytokine content Methods Using an artificial intelligence (AI) based approach, this study determined whether (i) accurate classification (ii) prediction intracellular IL-10 level was possible, using only features predictors for AI. a panel shape descriptors, assessed image-based original synthetic data two different datasets which CD14+ monocyte-derived macrophages generated from human peripheral blood monocytes were initially primed with GM-CSF or M-CSF followed by polarization specific stimuli presence/absence continuous M-CSF. Specifically, M0, M1 (GM-CSF-M1, TNFα/IFNγ-M1, GM-CSF/TNFα/IFNγ-M1) M2 (M-CSF-M2, IL-4-M2a, M-CSF/IL-4-M2a, IL-10-M2c, M-CSF/IL-10-M2c) examined. Results Phenotypes confirmed ELISA immunostaining CD markers. Variations techniques significantly changed multiple features, demonstrating that is highly sensitive, dynamic marker phenotype. data, cell alone yielded accuracy 93% 6 phenotypes (with M-CSF). A similarly high 95% reached (discontinuous M-CSF) measured time point. These comparably accuracies clearly validated here chosen AI-based approach. Quantitative also allowed data. Discussion Thus, machine learning morphology-based not classified but M2a M2c subtypes (iii) predicted among six phenotypes. This simple approach general strategy phenotyping any producing cell, help improve understanding biology

Language: Английский

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Effects of bone surface topography and chemistry on macrophage polarization

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 3, 2024

Abstract Surface structure plays a crucial role in determining cell behavior on biomaterials, influencing adhesion, proliferation, differentiation, as well immune cells and macrophage polarization. While grooves ridges stimulate M2 polarization pits bumps promote M1 polarization, these structures do not accurately mimic the real bone surface. Consequently, impact of mimicking surface topography remains unknown. Understanding synergistic sequential roles macrophages osteoimmunomodulation is for effective tissue engineering. Thus, exploring microstructure biomaterials critical. In this study, we aimed to sequentially activate using Poly- l -Lactic acid (PLA) membranes with topographical features mimicked through soft lithography technique. To topography, bovine femur was used model surface, were further modified collagen type-I hydroxyapatite microenvironment. determine effect conducted experimental analysis that contained estimating cytokine release profiles characterizing morphology. Our results demonstrated potential hydroxyapatite-deposited surface-mimicked PLA trigger polarizations, suggesting their ability achieve osteoimmunomodulatory engineering applications. Although studies are required completely investigate effects our provide valuable insights into advantages complex microenvironment surfaces.

Language: Английский

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Multispectral autofluorescence for label free classification of immune cell type and activation/polarization status

Scandinavian Journal of Immunology, Journal Year: 2025, Volume and Issue: 101(2)

Published: Feb. 1, 2025

Evaluating immune status is a challenging and time-consuming process that involves analysing various biomarkers through numerous assays. The sensitive label-free technique of multispectral imaging cell autofluorescence directly assessing the molecular composition cells to gather biological information. Cells were cultured in RPMI 1640 modified media supplemented with penicillin-streptomycin 10% foetal bovine serum at 37°C, 5% CO2 95% humidity. Activation differentiation was confirmed using immunofluorophores against relevant markers. Multispectral microscopy utilized defined spectral regions, which spanned excitation (345-476 nm) emission (414-675 wavelength ranges. In total, 56 distinct channels applied. These cover spectrum several fluorophores notably NAD(P)H flavins, whose concentrations depend on cellular metabolism. We identified signatures for characterizing from Jurkat, Ramos, THP-1, HL-60 lines. correspond four major types: T (Lymphocytes), B monocytes neutrophils. Moreover, our investigation explored potential identification both activated resting forms these cells, including discrimination M0, M1 M2 polarized macrophages. Classification accuracy ranged 92% 100% based receiver operator characteristic area under curve (ROC AUC) assessment. results indicate evaluation applicable characterization status. This includes assessment types their activation status, all achievable single non-invasive assay.

Language: Английский

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Polarized Tissue-Derived Macrophages Display Enhanced M2d Phenotype after Prolonged Stimulation with Adenosine A2A Receptor Agonist in the Presence of LPS

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 17, 2025

Background: Macrophages (Mφ) are innate immune cells known for their different activation phenotypes, classically described as falling within two broad categories, M1 and M2. The latter were originally alternatively activated M2 to differentiate them from cells. later classified into M2a (interleukin (IL)-4), M2b (immune complex), M2c (IL-10) M2d (5-(N-ethylcarboxamido) adenosine (NECA) + lipopolysaccharide (LPS)) based on inducing stimuli. Considering the established role of M2d/tumour-associated macrophage (TAM) cancer initiation proliferation, expanding knowledge characteristics can provide fundamental information Mφ targeted immunotherapy. precise characterization derived tissues has not been in detail. Methods: Our study focused spleen-derived macrophages (SpM), which also compared bone marrow-derived (BMDMs). Results: By investigating conditions M2d-specific stimulation employing various assays including functional tests, we show how (NECA LPS) polarization be affected by prolonged culture induce a phenotype that was clearly Conclusion: This work offers new insights properties primary following extended with LPS NECA.

Language: Английский

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Intranasal delivery of epigallocatechin gallate-laden platelet extracellular vesicles for mitigating retinal glaucoma

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113596 - 113596

Published: March 1, 2025

Language: Английский

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CaMKK2 Regulates Macrophage Polarization Induced by Matrix Stiffness: Implications for Shaping the Immune Response in Stiffened Tissues

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Macrophages are essential for immune responses and maintaining tissue homeostasis, exhibiting a wide range of phenotypes depending on their microenvironment. The extracellular matrix (ECM) is vital component that provides structural support organization to tissues, with stiffness acting as key regulator macrophage behavior. Using physiologically relevant 3D stiffening hydrogel models, it found increased alone promoted polarization toward pro-regenerative phenotype, mimicking the effect interleukin-4(IL-4) in softer matrices. Blocking Calcium/calmodulin-dependent kinase 2 (CaMKK2) selectively inhibited stiffness-induced without affecting IL-4-driven pathways. In functional studies, CaMKK2 deletion prevented M2-like/pro-tumoral caused by stiffening, which turn hindered tumor growth. murine wound healing model, loss impaired stiffness-mediated accumulation, ultimately disrupting vascularization. These findings highlight critical role mechanosensitive fate determination gene expression program, positioning this promising therapeutic target modulate pathologically stiff tissues.

Language: Английский

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