Poster abstracts
Poster number 42 submitted by Natalie Aloi
Macrophage dynamics and disease progression in Duchenne Muscular Dystrophy
Natalie Aloi (MCDB), Geremy Lerma (Molecular Genetics), Joseph Beljan (MCDB), Jared Talbot (University of Maryland School of Biology and Ecology)
Abstract:
Duchenne Muscular Dystrophy (DMD) is a devastating and fatal disease affecting 1 in 5000 males. Although the standard of care for DMD is treatment with immunosuppressive drugs, the immunopathology of DMD is poorly understood. Understanding immune cell behaviors and immune-directed signaling over the course of the disease is critical to development of more targeted and effective therapies. Macrophages comprise a large portion of the immune infiltrate in DMD and can be polarized towards a myriad of activation states that are distributed across two broad categories: pro-inflammatory (M1), and anti-inflammatory (M2). M2-polarized macrophages secrete TGF-β, a pro-fibrotic cytokine implicated in dystrophic muscle damage. Paradoxically, it is also known that promoting M2 polarization improves muscle pathology in DMD models. It is unclear how M2 macrophages provide a protective effect in DMD despite producing TGF-β. We are characterizing the role of macrophages in vivo in a well-established zebrafish DMD disease model. Confocal analyses of dystrophic larvae reveal that macrophages are actively recruited to dystrophic lesions early and clear from the site of injury as lesions resolve, but that macrophage behaviors change as the disease progresses. Additionally, the number of TGF- β -responsive cells, indicated by high levels of phosphorylated (activated) SMAD3 protein (pSMAD3) is elevated near dystrophic lesions early in disease progression. These data support the hypothesis that macrophages and macrophage-directed TGF-β signaling play an important role in DMD disease progression.
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Keywords: Duchenne Muscular Dystrophy, Macrophage, Zebrafish