IL-5 driven tissue eosinophils may limit muscle damage in Duchenne muscular dystrophy (mdx) mice

Authors

• AC Sek
• IA Moore
• K Pak
• JG Tidball
• HF Rosenberg

Abstract

Duchenne Muscular Dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and muscle inflammation. Eosinophils are prominent in muscle tissue at sites of inflammation and necrosis, although their specific contributions to muscle pathology are not clearly understood. In this study, we hypothesized that eosinophils are recruited in response to signals from necrotic muscle but are not necessarily tissue destructive. Furthermore, because eosinophils can display substantial plasticity, we hypothesized that eosinophil function in the muscle may depend on specific cues derived from the muscle microenvironment. To test these hypotheses, we evaluated pathology and characterized eosinophils in muscle tissue of: (1) mdx mice, which model DMD; (2) interleukin-5 transgenic (IL5Tg) mice, which have global eosinophilia; and (3) mdx-IL5Tg mice, in which the impact of the dystrophin mutation can be evaluated in the setting of IL5-driven hyper-eosinophilia. We established two key findings. First, eosinophil infiltration does not universally correlate with muscle damage. While we detected eosinophils in skeletal muscles of both mdx and IL-5Tg mice, we did not observe any muscle damage in the IL-5Tg mice. Second, eosinophils generated in response to IL-5 may function to limit mdx-associated muscle necrosis. In comparing mdx-IL5Tg mice with mdx mice, we detected reduced muscle pathology. Currently, we are utilizing RNA-sequencing to identify critical features that distinguish eosinophils in the muscle tissue of mdx, IL-5Tg, and mdx-IL5Tg mice. These studies will enhance understanding of the mechanisms by which IL5 and/or IL5-primed eosinophils limit dystrophic muscle damage and may ultimately suggest novel therapeutic strategies for DMD.

Scientific Focus Area: Immunology

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