IFIT3: a crucial mediator in innate immunity and tumor progression with therapeutic implications DOI Creative Commons
Rihan Wu, Hao Yang, Chunlei Liu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 24, 2025

Interferon-Induced Protein with Tetratricopeptide Repeats 3 (IFIT3) plays a dual role in innate immunity and tumor immunity, functioning as both viral defense molecule regulator of progression. This review explores the mechanisms through which IFIT3 modulates immune responses, including interferon signaling, RIG-I-like receptors, NF-κB pathway. facilitates evasion promotes inflammation-mediated growth by regulating checkpoints microenvironment, its emerging target for cancer immunotherapy opens new avenues therapeutic strategies. Finally, this paper underscores IFIT3's potential clinical applications modulation highlighting need further research on IFIT3-targeted therapies.

Language: Английский

Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies DOI Creative Commons
Z. L. Yuan,

Jiang De-cheng,

Mengzhu Yang

et al.

Orthopaedic Surgery, Journal Year: 2024, Volume and Issue: 16(3), P. 532 - 550

Published: Jan. 31, 2024

Osteoarthritis (OA) is the most common chronic degenerative joint disease in middle‐aged and elderly people, characterized by pain dysfunction. Macrophages are key players OA pathology, their activation state has been studied extensively. Various studies have suggested that macrophages might respond to stimuli microenvironment changing phenotypes pro‐inflammatory or anti‐inflammatory phenotypes, which called macrophage polarization. accumulate become polarized (M1 M2) many tissues, such as synovium, adipose tissue, bone marrow, mesenchymal tissues joints, while resident well other stromal cells, including fibroblasts, chondrocytes, osteoblasts, form function an integrated unit. In this study, we focus exclusively on synovial macrophages, tissue osteoclasts, investigate roles development of OA. We review recent findings related polarization OA, pathogenesis, molecular pathways, therapeutics. summarize several signaling pathways reprogramming NF‐κB, MAPK, TGF‐β, JAK/STAT, PI3K/Akt/mTOR, NLRP3. Of note, despite increasing availability treatments for osteoarthritis, like intra‐articular injections, surgery, cellular therapy, demand more effective clinical therapies remained steady. Therefore, also describe current prospective therapeutic methods deem be a target, physical stimulus, chemical compounds, biological molecules, enhance cartilage repair alleviate progression

Language: Английский

Citations

20
Therapeutic role of hucMSC-sEV-enriched miR-13896 in cisplatin-induced acute kidney injury through M2 macrophage polarization DOI Creative Commons
Can Jin, Peipei Wu, Wei Wu

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Feb. 24, 2025

Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hucMSC-sEV) have recently garnered attention as a potential therapeutic approach for kidney diseases with anti-inflammatory effects. Infiltrated macrophages play an important role in facilitating tissue regeneration. However, the intricate regulatory effects of hucMSC-sEV on during cisplatin-induced acute injury (AKI) remain unknown. In this study, we uncovered that exhibited potent anti-inflammation and effectively inhibited polarization M1 phenotype macrophages. Mechanically, miRNA sequencing analysis qRT-PCR indicated novel miRNA, named miR-13896, was enriched hucMSC-sEV. When transfected miR-13896 mimic, displayed M2 elevated levels Arg1 IL-10, while inhibitor promoted phenotype. Furthermore, firstly established repressed Tradd expression by targeting its 3' untranslated region subsequently NF-κB signaling pathway Additionally, to improve effects, were engineered through electroporation, which resulted promoting macrophages, inhibiting inflammatory factors, enhancing repair. Conclusively, our findings provide insights into mechanisms underlying AKI, also highlighting electroporation promising strategy treating AKI.

Language: Английский

Citations

3
Targeting conserved TIM3 + VISTA + tumor-associated macrophages overcomes resistance to cancer immunotherapy DOI Creative Commons
Isaure Vanmeerbeek, Stefan Naulaerts, Jenny Sprooten

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(29)

Published: July 19, 2024

Despite the success of immunotherapy, overcoming immunoresistance in cancer remains challenging. We identified a unique niche tumor-associated macrophages (TAMs), coexpressing T cell immunoglobulin and mucin domain–containing 3 (TIM3) V-domain suppressor activation (VISTA), that dominated human mouse tumors resistant to most currently used immunotherapies. TIM3 + VISTA TAMs were sustained by IL-4–enriching with low (neo)antigenic cell–depleted features. showed an anti-inflammatory protumorigenic phenotype coupled inability sense type I interferon (IFN). This was established cells succumbing immunogenic death (ICD). Dying not only triggered autocrine IFNs but also exposed HMGB1/VISTA engaged TIM3/VISTA on suppress paracrine IFN-responses. Accordingly, blockade synergized paclitaxel, ICD-inducing chemotherapy, repolarize proinflammatory killed via tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) signaling. propose targeting overcome immunoresistant tumors.

Language: Английский

Citations

13
Lipid-associated macrophages between aggravation and alleviation of metabolic diseases DOI Creative Commons
Ruonan Xu, Nemanja Vujić, Valentina Bianco

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(11), P. 981 - 995

Published: May 4, 2024

Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals obesity, liver lesions steatosis and steatohepatitis, the intestinal lamina propria. LAMs can also emerge metabolically demanding microenvironment certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, self-renewal, and, ultimately, their acute chronic functional impact on development diseases. Further studies need clarify whether under which circumstances drive progression or resolution how phenotype be modulated ameliorate disorders.

Language: Английский

Citations

12
Self-Adapting Biomass Hydrogel Embodied with miRNA Immunoregulation and Long-Term Bacterial Eradiation for Synergistic Chronic Wound Therapy DOI
Jun Wu, Yang‐Chang Wu, Heng Tang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(28), P. 18379 - 18392

Published: July 2, 2024

Chronic wound rescue is critical for diabetic patients but challenging to achieve with a specific and long-term strategy. The prolonged bacterial inflammation particularly prevalent in hyperglycemia-induced wounds, usually leading severe tissue damage. Such trend could further suffer from an environmental suitability provided by macrophages persisting Staphylococcus aureus (S. aureus) even deteriorate their mutual reinforcement. However, the strategy of both suppressing bacteria growth immunoreprogramming inflammatory type break vicious harm healing still lacking. Here, self-adapting biomass carboxymethyl chitosan (CMC) hydrogel comprising immunomodulatory nanoparticles reported Gram-negative/Gram-positive elimination anti-inflammatory cytokines induction ameliorate cutaneous microenvironment. Mechanistically, antibacterial peptides CMCs synergistically result inhibition against methicillin-resistant S. (MRSA) over period 7 days, miR-301a reprograms M2 macrophage via PTEN/PI3Kγ/mTOR signaling pathway, consequently mitigating promoting angiogenesis rats. In this vein, immunoregulatory promising all-biomass dressing ensuring biocompatibility, providing perspective regenerate damaged tissue, repairing chronic wounds on skin.

Language: Английский

Citations

9
Innate immune cells link dietary cues to normal and abnormal metabolic regulation DOI
Peng Zhang, Kosuke Watari, Michael Karin

et al.

Nature Immunology, Journal Year: 2025, Volume and Issue: 26(1), P. 29 - 41

Published: Jan. 1, 2025

Language: Английский

Citations

1
A Feedback Loop Driven by H4K12 Lactylation and HDAC3 in Macrophages Regulates Lactate‐Induced Collagen Synthesis in Fibroblasts Via the TGF‐β Signaling DOI Creative Commons
Ying Zou,

Mibu Cao,

Meiling Tai

et al.

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

Published: Feb. 13, 2025

Abstract The decrease in fibroblast collagen is a primary contributor to skin aging. Lactate can participate synthesis through lysine lactylation by regulating gene transcription. However, the precise mechanism which lactate influences requires further investigation. This study demonstrates that depletion of macrophages mitigates stimulating effect on fibroblasts. Through joint CUT&Tag and RNA‐sequencing analyses, feedback loop between H4K12 (H4K12la) histone deacetylase 3 (HDAC3) drives lactate‐induced are identified. Macrophages uptake extracellular via monocarboxylate transporter‐1 (MCT1), leading an up‐regulation H4K12la levels KAT5‐KAT8‐dependent response Poly‐L‐Lactic Acid (PLLA) stimulation, source low concentration persistent lactate, thereby promoting Furthermore, enriched at promoters TGF‐β1 TGF‐β3, enhancing their Hyperlactylation inhibits expression eraser HDAC3, while activation HDAC3 reduces suppresses In conclusion, this illustrates play critical role skin, targeting lactate‐H4K12la‐HDAC3‐TGF‐β axis may represent novel approach for production combat

Language: Английский

Citations

1
Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets DOI Creative Commons

Fan Guan,

Ruixuan Wang,

Zhenjie Yi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

Citations

1
Recent advances in targeted therapy for inflammatory vascular diseases DOI
Kaiwen Zhao, Zan Zeng,

Yuzhen He

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 730 - 750

Published: July 3, 2024

Language: Английский

Citations

7
Regulation of macrophage activation by lactylation in lung disease DOI Creative Commons
Yungeng Wei, Hua Guo,

Shixing Chen

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Lactylation is a process where lactate, cellular metabolism byproduct, added to proteins, altering their functions. In the realm of macrophage activation, lactylation impacts inflammatory response and immune regulation. Understanding effects on activation vital in lung diseases, as abnormal function are pivotal conditions like pneumonia, pulmonary fibrosis, COPD, cancer. This review explores concept lactylation, its regulation recent research progress diseases. It offers new insights into disease pathogenesis potential therapeutic targets.

Language: Английский

Citations

7