Poster abstracts

Poster number 2 submitted by Natalie Aloi

Macrophage dynamics and disease progression in Duchenne Muscular Dystrophy

Natalie M 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 5000 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 targeted and effective therapies. Macrophages, which comprise a large portion of the immune infiltrate in DMD, can be polarized towards a myriad of polarization states broadly categorized as pro-inflammatory (M1), or anti-inflammatory (M2). 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, early in disease progression, macrophages are actively recruited to dystrophic lesions and clear from the site of injury during lesion resolution, but that this behavior changes as the disease progresses. 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 and macrophage-directed TGF-β signaling may have an important role in disease progression in DMD.

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Keywords: Duchenne Muscular Dystrophy, Macrophage, Zebrafish