The multifaceted role of macrophages in homeostatic and injured skeletal muscle DOI Creative Commons
Xingyu Wang, Lan Zhou

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 25, 2023

Skeletal muscle is essential for body physical activity, energy metabolism, and temperature maintenance. It has excellent capabilities to maintain homeostasis regenerate after injury, which indispensably relies on stem cells, satellite cells (MuSCs). The quiescence, activation, differentiation of MuSCs are tightly regulated in homeostatic regenerating muscles. Among the important regulators intramuscular macrophages, functionally heterogeneous with different subtypes present a spatiotemporal manner regulate balance MuSC statuses. During chronic injury aging, macrophages often undergo aberrant turn disrupts regenerative repair. Growing evidence suggests that activation mainly triggered by altered microenvironment. trained immunity affects myeloid progenitors during hematopoiesis may also contribute. Aged immune system contribute, part, aging-related sarcopenia compromised skeletal As actively involved progression many diseases, manipulating their functional become promising therapeutic approach, requires comprehensive knowledge cellular molecular mechanisms underlying diverse activation. To this end, we discuss here current multifaceted role homeostasis,

Language: Английский

Interleukin-1β polarization in M1 macrophage mediates myocardial fibrosis in diabetes DOI Creative Commons
Wenli Guo, Chen Yang, Jiawei Zou

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111858 - 111858

Published: March 15, 2024

Language: Английский

Citations

10
Osteopontin/SPP1: a potential mediator between immune cells and vascular calcification DOI Creative Commons

Yanli Zhao,

Zujuan Huang,

Limei Gao

et al.

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

Published: June 11, 2024

Vascular calcification (VC) is considered a common pathological process in various vascular diseases. Accumulating studies have confirmed that VC involved the inflammatory response heart disease, and SPP1+ macrophages play an important role this process. In VC, focused on physiological functions of macrophages, such as pro-inflammatory or anti-inflammatory cytokines pro-fibrotic vesicles. Additionally, activated lymphocytes highly express SPP1 atherosclerotic plaques, which promote formation fatty streaks plaque development, also plaques results failure, but crosstalk between SPP1-mediated immune cells has not been adequately addressed. review, we summarize regulatory effect T cells, dendritic different organs' could be potential therapeutic target for VC.

Language: Английский

Citations

10
Macrophage and fibroblast trajectory inference and crosstalk analysis during myocardial infarction using integrated single-cell transcriptomic datasets DOI Creative Commons

Da Ke,

Mingzhen Cao,

Jian Ni

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 12, 2024

Abstract Background Cardiac fibrosis after myocardial infarction (MI) has been considered an important part of cardiac pathological remodeling. Immune cells, especially macrophages, are thought to be involved in the process and constitute a niche with fibroblasts promote fibrosis. However, diversity variability macrophages make it difficult accurately depict interconnections. Methods We collected reanalyzed scRNA-seq snRNA-seq datasets from 12 different studies. Differentiation trajectories these subpopulations MI injury were analyzed by using scVelo, PAGA Slingshot. used CellphoneDB NicheNet infer fibroblast-macrophage interactions. Tissue immunofluorescence staining vitro experiments validate our findings. Results discovered two subsets ECM-producing fibroblasts, reparative (RCFs) matrifibrocytes, which appeared at times exhibited transcriptional profiles. also observed that CTHRC1 + represent activated fibroblast chronic disease states. identified macrophage subset expressing genes signature SAMs conserved both human mouse hearts. Meanwhile, SPP1 hi predominantly found early stages MI, cell communication analysis indicated macrophage-RCFs interactions mainly collagen deposition scar formation. Conclusions Overall, this study comprehensively dynamics specific formation deposition.

Language: Английский

Citations

10
Profibrotic Subsets of SPP1+ Macrophages and POSTN+ Fibroblasts Contribute to Fibrotic Scarring in Acne Keloidalis DOI
Yi‐Kai Hong, Daw‐Yang Hwang, Chao‐Chun Yang

et al.

Journal of Investigative Dermatology, Journal Year: 2024, Volume and Issue: 144(7), P. 1491 - 1504.e10

Published: Jan. 11, 2024

Language: Английский

Citations

9
Macrophage diversity in human cancers: New insight provided by single-cell resolution and spatial context DOI Creative Commons
Militsa Rakina, Irina Larionova, Julia Kzhyshkowska

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28332 - e28332

Published: March 22, 2024

M1/M2 paradigm of macrophage plasticity has existed for decades. Now it becomes clear that this dichotomy doesn't adequately reflect the diversity phenotypes in tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a major population innate immune cells TME promotes cell proliferation, angiogenesis and lymphangiogenesis, invasion metastatic niche formation, as well response to anti-tumor therapy. However, fundamental restriction therapeutic TAM targeting is limited knowledge about specific states distinct human cancer types. Here we summarized results most recent studies use advanced technologies (e.g. single-cell RNA sequencing spatial transcriptomics) allowing decipher novel functional subsets TAMs numerous cancers. The transcriptomic profiles these their clinical significance were described. We emphasized characteristics subpopulations – TREM2+, SPP1+, MARCO+, FOLR2+, SIGLEC1+, APOC1+, C1QC+, others, which have been extensively characterized several cancers, associated with prognosis. Spatial transcriptomics defined interactions between other types, especially fibroblasts, tumors. methods also applied identify markers immunotherapy response, expressed by or macrophage-abundant regions. highlighted perspectives techniques utilize single resolution investigating new ligand-receptor effective based on TAM-targeting.

Language: Английский

Citations

9
Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity DOI
Marie Dominique Ah Kioon, Paôline Laurent, Vidyanath Chaudhary

et al.

Immunological Reviews, Journal Year: 2024, Volume and Issue: 323(1), P. 241 - 256

Published: March 29, 2024

Summary The discovery of toll‐like receptors (TLRs) and the subsequent recognition that endogenous nucleic acids (NAs) could serve as TLR ligands have led to essential insights into mechanisms healthy immune responses well pathogenic relevant systemic autoimmune inflammatory diseases. In lupus erythematosus, sclerosis, rheumatoid arthritis, NA‐containing complexes ligands, with distinct implications depending on additional stimuli available. Plasmacytoid dendritic cells (pDCs), robust producers type I interferon (IFN‐I), are providing critical TLR‐mediated tissue repair, generation inflammation, autoimmunity fibrosis, processes central pathogenesis many this review, we describe recent data characterizing role platelets NA‐binding chemokines in modulation signaling pDCs, for how IFN‐I products pDCs contribute inflammation wound healing by monocyte/macrophages. Chemokine modulators B cell tolerance interactions between metabolic pathways also considered. their contribution diseases suggest new opportunities identification novel therapeutic targets.

Language: Английский

Citations

9
METTL3 Potentiates M2 Macrophage‐Driven MMT to Aggravate Renal Allograft Fibrosis via the TGF‐β1/Smad3 Pathway DOI Creative Commons

Qinfan Yao,

Xiaoxiao Zheng, Xinyi Zhang

et al.

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

Published: Jan. 27, 2025

Abstract METTL3, a key enzyme in N6‐methyladenosine (m6A) modification, plays crucial role the progression of renal fibrosis, particularly chronic active allograft rejection (CAR). This study explored mechanisms by which METTL3 promotes focusing on its macrophage‐to‐myofibroblast transition (MMT). Using comprehensive experimental approach, including TGF‐β1‐induced MMT cell models, conditional knockout (METTL3 KO) mice, and biopsy samples from patients with CAR, investigates involvement METTL3/Smad3 axis driving fibrosis during episodes CAR. We found that elevated m6A modification levels strongly correlated enhanced increased fibrotic severity. significantly Smad3, decreased Smad3 expression, inhibited M2‐driven MMT. knockdown siRNA (siSmad3) further MMT, while overexpression rescued inhibitory effects silencing, restoring tissue damage. Additionally, inhibitor STM2457 effectively reversed alleviated damage These findings highlight enhances CAR promoting TGF‐β1/Smad3 axis, suggesting is promising therapeutic target for mitigating

Language: Английский

Citations

1
SPP1hi macrophages, NKG7 T cells, CCL5hi fibroblasts, and IgM plasma cells are dominant features of necrobiosis DOI Creative Commons
Stephanie T. Le, Alina I. Marusina, Alexander A. Merleev

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: 10(4)

Published: Feb. 23, 2025

Necrobiosis is a histologic term used to describe abnormal deposits of "degenerating" collagen within the skin. It can be found as an incidental finding in various granulomatous conditions, but hallmark necrobiosis lipoidica (NL) and necrobiotic xanthogranuloma (NXG). There limited prior research on necrobiosis. Here, we employed single-cell analysis lesional nonlesional skin study pathophysiology Our findings demonstrate that characterized by SPP1hi macrophages expressing MARCO; NKG7-expressing effector CD8+ T cells coexpressing CCL5, IFNG, GZMs, PRF1; CCL5hi fibroblasts CXCL9, diverse collagens (e.g., COL4A4, COL11A1, COL8A1), TIMP1; IGHM-expressing plasma cells. Integrative signaling ligands receptor expression identified strong cell-cell communication between NKG7+ cells, fibroblasts, SPP1-expressing macrophages. In contrast, these cell populations were not dominant features systemic sclerosis, another deposition disease. Furthermore, although detectable sarcoidosis, IFNG-expressing more defining feature sarcoidosis compared with NL NXG. From findings, speculate results from ECM proteins through process driven CCL5-expressing

Language: Английский

Citations

1
SPP1 macrophages across diseases: A call for reclassification? DOI Creative Commons
Alessio Reggio, Claudia Fuoco, Rebecca Deodati

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 6, 2025

SPP1+ macrophages, characterized by elevated expression of the osteopontin gene (secreted phosphoprotein 1, SPP1), have emerged as key players in various pathological contexts, including aging, chronic inflammatory diseases, and cancer. While frequently classified a subclass tumor-associated macrophages oncological settings, their presence noncancer conditions, such aging-related disorders muscular suggests broader role beyond tumors. These share conserved traits, fibrosis promotion, extracellular matrix remodeling, immune modulation, often linked to poor clinical outcomes. This perspective explores multifaceted roles across diseases advocates for reclassification distinct macrophage subtype associated with or prolonged inflammation. Recognizing cross-disease relevance could reshape biology inform targeted therapeutic strategies.

Language: Английский

Citations

1
Innate Immunity and Asthma Exacerbations: Insights From Human Models DOI
Jehan Alladina, Benjamin D. Medoff, Christina Schofield

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: March 1, 2025

ABSTRACT Asthma is a common chronic respiratory disease characterized by the presence of airway inflammation, hyperresponsiveness, and mucus hypersecretion. Repeated asthma exacerbations can lead to progressive remodeling irreversible airflow obstruction. Thus, understanding preventing are paramount importance. Although multiple endotypes exist, most often driven type 2 inflammation. New therapies that target specific mediators have been shown reduce frequency but incompletely effective in significant number asthmatics. Furthermore, it remains unknown whether current treatments sustained changes or if targeting additional pathways may be necessary achieve remission. Activation innate immunity initial event inflammatory sequence occurs during an exacerbation. However, there continue critical gaps our immune response exacerbating factors. In this review, we summarize role methods used study them. We also identify potential novel therapeutic targets for future areas investigation.

Language: Английский

Citations

1