Genetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically DOI Creative Commons
mingming zhao, Dragana Janković, Verena M. Link

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 25, 2025

Abstract How macrophages in the tissue environment integrate multiple stimuli depends on genetic background of host, but this is still poorly understood. We investigate IL-4 activation male C57BL/6 and BALB/c strain specific vivo tissue-resident (TRMs) from peritoneal cavity. TRMs are more transcriptionally responsive to stimulation, with induced genes associated super enhancers, topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling reveals enrichment NF-κB, IRF, STAT motifs. Additionally, IL-4-activated demonstrate an augmented synergistic response upon vitro lipopolysaccharide (LPS) exposure, despite naïve displaying a robust transcriptional LPS. Single-cell RNA sequencing (scRNA-seq) analysis mixed bone marrow chimeras indicates that differences synergy cell intrinsic within same environment. Hence, variation alters IL-4-induced epigenetic reprogramming resulting responses LPS exposure.

Language: Английский

The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages DOI Creative Commons

Buyun Dang,

Qingxiang Gao, Lishan Zhang

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(5), P. 112471 - 112471

Published: May 1, 2023

T helper type 2 (Th2) cytokine-activated M2 macrophages contribute to inflammation resolution and wound healing. This study shows that IL-4-primed exhibit a stronger response lipopolysaccharide stimulation while maintaining signature gene expression. Metabolic divergence between canonical non-canonical proinflammatory-prone (M2INF) occurs after the IL-4Rα/Stat6 axis. Glycolysis supports Hif-1α stabilization proinflammatory phenotype of M2INF macrophages. Inhibiting glycolysis blunts accumulation phenotype. Wdr5-dependent H3K4me3 mediates long-lasting effect IL-4, with Wdr5 knockdown inhibiting Our results also show induction by IL-4 intraperitoneal injection transferring confer survival advantage against bacterial infection in vivo. In conclusion, our findings highlight previously neglected role broaden understanding IL-4-mediated physiological changes. These have immediate implications for how Th2-skewed infections could redirect disease progression pathogen infection.

Language: Английский

Citations

55
Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats DOI Creative Commons
Xin Qiao, Jie Tang, Lei Dou

et al.

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 4683 - 4703

Published: Aug. 1, 2023

Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, been found be closely associated with tissue regeneration. Periodontitis is an immune inflammation and destructive disease caused by plaque, resulting in alveolar bone loss periodontal epithelial destruction. It not clear whether DPSC-EXO can used as effective therapy for The purpose this study was only verify the effect on reducing periodontitis promoting regeneration, but also reveal possible mechanism.DPSC-EXO isolated ultracentrifugation. Then it characterized transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) Western Blot. In vitro, ligament cells (PDLSCs) were treated DPSC-EXO, abilities cell proliferation, migration osteogenic potential evaluated. Furthermore, we detected expression IL-1β, TNF-αand key proteins IL-6/JAK2/STAT3 signaling pathway after simulating inflammatory environment LPS. addition, polarization phenotype macrophages detected. vivo, experimental rats established or PBS. After 4 weeks, maxillae collected micro-CT histological staining.DPSC-EXO promoted osteogenesis PDLSCs vitro. regulated inhibiting during acute stress. results showed that could polarize from M1 M2 phenotype. effectively reduce promote healing epithelium periodontitis.DPSC-EXO plays important role This provides a promising acellular periodontitis.

Language: Английский

Citations

45
Macrophage plasticity: signaling pathways, tissue repair, and regeneration DOI Creative Commons
Lingfeng Yan, Jue Wang,

Xin Cai

et al.

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

Citations

28
Macrophage innate training induced by IL-4 and IL-13 activation enhances OXPHOS driven anti-mycobacterial responses DOI Creative Commons
Mimmi L. E. Lundahl, Morgane Mitermite, Dylan G. Ryan

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Sept. 29, 2022

Macrophages are a highly adaptive population of innate immune cells. Polarization with IFNγ and LPS into the ‘classically activated’ M1 macrophage enhances pro-inflammatory microbicidal responses, important for eradicating bacteria such as Mycobacterium tuberculosis . By contrast, ‘alternatively M2 macrophages, polarized IL-4, oppose bactericidal mechanisms allow mycobacterial growth. These activation states accompanied by distinct metabolic profiles, where macrophages favor near exclusive use glycolysis, whereas up-regulate oxidative phosphorylation (OXPHOS). Here, we demonstrate that IL-4 IL-13 counterintuitively induces protective memory against challenge. In human murine models, prior IL-4/13 cytokine secretion in response to secondary stimulation ligands. our model, enhanced killing capacity is also demonstrated. Despite this switch phenotype, trained do not M1-typical metabolism, instead retaining heightened OXPHOS. Moreover, inhibition OXPHOS oligomycin, 2-deoxy glucose or BPTES all impeded responses from macrophages. Lastly, work identifies IL-10 attenuates training, impeding mechanisms. summary, provides new unexpected insight alternative context infection.

Language: Английский

Citations

54
Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke DOI Creative Commons
Lei Li,

Shu-qi Cheng,

Yuqin Sun

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112617 - 112617

Published: June 1, 2023

Neutrophil aggregation and clearance are important factors affecting neuroinflammatory injury during acute ischemic stroke. Emerging evidence suggests that energy metabolism is essential for microglial functions, especially phagocytosis, which determines the degree of brain injury. Here, we demonstrate Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenic acid (DHA), promotes phagocytosis neutrophils by microglia, thereby reducing neutrophil accumulation in alleviating neuroinflammation brain. Further studies reveal RvD1 reprograms glycolysis to oxidative phosphorylation (OXPHOS), providing sufficient phagocytosis. Moreover, enhances glutamine uptake stimulates glutaminolysis support OXPHOS boost ATP production depending on adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Overall, our results promote after These findings may guide perspectives stroke therapy modulating immunometabolism.

Language: Английский

Citations

27
Multifaceted mitochondria in innate immunity DOI Creative Commons
Eloïse Marques,

Robbin Kramer,

Dylan G. Ryan

et al.

npj Metabolic Health and Disease, Journal Year: 2024, Volume and Issue: 2(1)

Published: May 27, 2024

Abstract The ability of mitochondria to transform the energy we obtain from food into cell phosphorylation potential has long been appreciated. However, recent decades have seen an evolution in our understanding mitochondria, highlighting their significance as key signal-transducing organelles with essential roles immunity that extend beyond bioenergetic function. Importantly, retain bacterial motifs a remnant endosymbiotic origin are recognised by innate immune cells trigger inflammation and participate anti-microbial defence. This review aims explore how mitochondrial physiology, spanning oxidative (OxPhos) signalling nucleic acids, metabolites, lipids, influences effector functions phagocytes. These myriad include macrophage polarisation, efferocytosis, anti-bactericidal activity, antigen presentation, signalling, cytokine regulation. Strict regulation these processes is critical for organismal homeostasis when disrupted may cause injury or contribute disease. Thus, expanding body literature, which continues highlight central role system, provide insights development next generation therapies inflammatory diseases.

Language: Английский

Citations

16
Short-chain fatty acids reverses gut microbiota dysbiosis-promoted progression of glioblastoma by up-regulating M1 polarization in the tumor microenvironment DOI
Mengnan Zhou,

Jianqi Wu,

Yang Shao

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 141, P. 112881 - 112881

Published: Aug. 18, 2024

Language: Английский

Citations

10
hCeO2@CA-074Me Nanoparticles Alleviate Inflammation and Improve Osteogenic Microenvironment by Regulating the CTSB-NLRP3 Signaling Pathway DOI Creative Commons

Zhaojun Niu,

Xiaomin Xia, Zhimin Zhang

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 161 - 179

Published: Jan. 1, 2025

Background: It is well established that the interaction between osteogenesis and inflammation can impact bone tissue regeneration. The use of nanoparticles to treat alleviate at molecular level has potential improve osteogenic microenvironment serve as a therapeutic approach. Methods: We have synthesized new hollow cerium oxide doped with cathepsin B inhibitor (CA-074Me) create novel h CeO 2 @CA-074Me NPs. characterized surface morphology physicochemical properties Macrophage RAW 264.7 was cultured NPs using P. gingivalis- LPS ( P.g -LPS) stimulation model inflammation. RT-PCR Western blot analysis employed evaluate effects on macrophage phenotype CTSB-NLRP3 signaling pathway. To further investigate inflammatory microenvironment, MC3T3-E1 cells were -LPS an in vitro conditions under then co-cultured for 7, 14, 21 d. ability evaluated ALP staining, quantitative analysis, alizarin red analysis. Results: Findings clearly demonstrated could effectively reduce production ROS inhibited signal pathway, thereby significantly attenuating damage caused by cellular response. also induce polarization macrophages towards anti-inflammatory M2 phenotype. Additionally, results confirmed inhibit ameliorate thus promoting cells. Conclusion: synthetic able modify simultaneously inhibiting pathway regulating through their scavenge ROS. Based these findings, our study may offer promising approach managing damage. Keywords: nanoparticles, CTSB, NLRP3, inflammation, regeneration,

Language: Английский

Citations

1
Sulforaphane promotes diabetic wound healing by regulating macrophage efferocytosis and polarization DOI
Yumeng Huang,

Beizhi Wang,

Zhouji Ma

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114243 - 114243

Published: Feb. 11, 2025

Language: Английский

Citations

1
Interrelation of adipose tissue macrophages and fibrosis in obesity DOI Creative Commons
Norma Dahdah,

Carmen Tercero‐Alcázar,

Marı́a M. Malagón

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 225, P. 116324 - 116324

Published: May 28, 2024

Obesity is characterized by adipose tissue expansion, extracellular matrix remodelling and unresolved inflammation that contribute to insulin resistance fibrosis. Adipose macrophages represent the most abundant class of immune cells in could be key mediators adipocyte dysfunction fibrosis obesity. Although macrophage activation states are classically defined M1/M2 polarization nomenclature, novel studies have revealed a more complex range phenotypes response external condition or surrounding microenvironment. Here, we discuss plasticity (ATMs) their microenvironment obesity, with special focus on infiltration polarization, contribution A better understanding role ATMs as regulators may provide therapeutic strategies against obesity associated metabolic diseases.

Language: Английский

Citations

8