Poster abstracts

Poster number 49 submitted by Natalie Aloi

Immune cells direct signaling and disease progression in a zebrafish model of 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, universally fatal disease affecting 1 in 3000 males. Although the standard of care for DMD is treatment with immunosuppressive drugs, the immunopathology of DMD is poorly understood. Understanding the behavior of immune cells and immune-directed signaling in DMD is critical to the development of more effective therapies. Macrophages, which comprise a large portion of the immune infiltrate in DMD, can be polarized towards a pro-inflammatory M1 or an anti-inflammatory M2 phenotype. M2 polarized macrophages secrete TGF-β, a pro-fibrotic cytokine implicated in dystrophic muscle damage. However, promoting M2 polarization improves muscle pathology in models of DMD. It is unclear how M2 macrophages provide a protective effect in DMD despite producing TGF-β. Ease of imaging and amenability to drug treatment make zebrafish larvae an ideal model to study macrophages in vivo. Our confocal analysis of dystrophic larvae reveals that macrophages are actively recruited to dystrophic lesions and clear from the site of injury during lesion resolution. Staining for the phosphorylated SMAD3 protein (pSMAD3), which marks cells responding to TGF-β, shows an elevated level of TGF-β-responsive cells and macrophages near dystrophic lesions. These data suggest that macrophages may indeed play a central role in the regulation of TGF-β signaling in dystrophic tissues.

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Keywords: Duchenne Muscular Dystrophy, Macrophage, Zebrafish