ArticleHuman molecular genetics2015
Toll-like receptor 4 ablation in mdx mice reveals innate immunity as a therapeutic target in Duchenne muscular dystrophy.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Pooled it
- Systemic regeneration medicines for muscular dystrophy: progress and challenges in pro-regenerative drug development.Cell regeneration (London, England) · 2026Review
- CTLA4-Ig reduces proliferation and inflammatory gene expression in muscle fibroblasts, corresponding to less fibrosis and inflammation inAmerican journal of physiology. Cell physiology · 2026Article
- Convergent innate immune and regulated cell-death pathways in selected myopathies.Frontiers in immunology · 2026Review
- The miR-30c-5p/SOCS3 axis is a potential driver of inflammation and metabolic imbalance in Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2026Article
- Intercellular communication from myotubes to fibroblasts is differentially impacted by mineralocorticoid receptor signaling and muscular dystrophy.Cell communication and signaling : CCS · 2025Article
- Review
- Organ Crosstalk: The Role of Spleen.Phenomics (Cham, Switzerland) · 2025Review
- Cytotoxic T-Lymphocyte-Associated Protein 4 Fused to a Modified Fragment of IgG1 Reduces Muscle Fiber Damage in a Model of Duchenne Muscular Dystrophy by Attenuating Proinflammatory Gene Expression in Myeloid Lineage Cells.The American journal of pathology · 2025Article
- HMGB1 in Septic Muscle Atrophy: Roles and Therapeutic Potential for Muscle Atrophy and Regeneration.Journal of cachexia, sarcopenia and muscle · 2025Review
- Stem/progenitor cell-based therapy for Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2025Review
- The Gut Microbiota Involvement in the Panorama of Muscular Dystrophy Pathogenesis.International journal of molecular sciences · 2024Review
- Macrophages in the Context of Muscle Regeneration and Duchenne Muscular Dystrophy.International journal of molecular sciences · 2024Review
- High mobility group box 1 (HMGB1) is a potential disease biomarker in cell and mouse models of Duchenne muscular dystrophy.Biology open · 2024Article
- IL-33 Facilitates Fibro-Adipogenic Progenitors to Establish the Pro-Regenerative Niche after Muscle Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Identification of hub genes and therapeutic siRNAs to develop novel adjunctive therapy for Duchenne muscular dystrophy.BMC musculoskeletal disorders · 2024Article
- Regenerative inflammation: When immune cells help to re-build tissues.The FEBS journal · 2024Review
- How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?Proteomes · 2024Article
- Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Histone deacetylase inhibition with givinostat: a multi-targeted mode of action with the potential to halt the pathological cascade of Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2024Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Toll-like receptor 4 (TLR4) recognizes specific structural motifs associated with microbial pathogens and also responds to certain endogenous host molecules associated with tissue damage. In Duchenne muscular dystrophy (DMD), inflammation plays an important role in determining the ultimate fate of dystrophic muscle fibers. In this study, we used TLR4-deficient dystrophic mdx mice to assess the role of TLR4 in the pathogenesis of DMD. TLR4 expression was increased and showed enhanced activation following agonist stimulation in mdx diaphragm muscle. Genetic ablation of TLR4 led to significantly increased muscle force generation in dystrophic diaphragm muscle, which was associated with improved histopathology including decreased fibrosis, as well as reduced pro-inflammatory gene expression and macrophage infiltration. TLR4 ablation in mdx mice also altered the phenotype of muscle macrophages by inducing a shift toward a more anti-inflammatory (iNOS(neg) CD206(pos)) profile. In vitro experiments confirmed that lack of TLR4 is sufficient to influence macrophage activation status in response to classical polarizing stimuli such as IFN-gamma and IL-4. Finally, treatment of dystrophic mice with glycyrrhizin, an inhibitor of the endogenous TLR4 ligand, high mobility group box (HMGB1), also pointed to involvement of the HMGB1-TLR4 axis in promoting dystrophic diaphragm pathology. Taken together, our findings reveal TLR4 and the innate immune system as important players in the pathophysiology of DMD. Accordingly, targeting either TLR4 or its endogenous ligands may provide a new therapeutic strategy to slow disease progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.