Exploration of Immunology, Journal Year: 2025, Volume and Issue: 5
Published: April 16, 2025
Monogenic muscular dystrophies (MDs), such as Duchenne dystrophy (DMD) and limb-girdle (LGMD), are characterized by chronic inflammation, progressive fibrosis, impaired muscle regeneration. Central to these pathological processes macrophages, which exhibit dynamic polarization states that influence the dystrophic microenvironment. In early disease stages, macrophages support tissue repair regeneration, but inflammation skews their activity toward pro-fibrotic phenotypes, driving excessive extracellular matrix (ECM) deposition dysfunction. Macrophages also interact with other immune cells, T cells neutrophils, non-immune including fibroblasts satellite regulate inflammatory fibrotic responses. These interactions establish a dysregulated environment exacerbates damage impairs effective Preclinical studies using mdx mouse model of DMD highlight critical role in sustaining particularly through transforming growth factor-beta (TGF-β) signaling fibro-adipogenic progenitor (FAP) activation. Therapeutically, targeting offers significant potential mitigate progression. Strategies include modulating macrophage pro-regenerative M2 phenotype, inhibiting recruitment via chemokine signaling, reprogramming metabolism oxidative phosphorylation mitochondrial function. Additionally, anti-fibrotic interventions TGF-β or macrophage-FAP crosstalk have shown promise reducing ECM preserving architecture. this review, we curate relevant provide insights into molecular mechanisms governing behavior muscle. Herein, discuss how emerging therapeutic strategies macrophage-mediated pathways can be leveraged enhance improve clinical outcomes.
Language: Английский