A role for group 2 innate lymphoid cells in muscular dystrophy
| Autor: | Jenna Kastenschmidt |
|---|---|
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 202:183.20-183.20 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder characterized by progressive myofiber degeneration and chronic inflammation. Asynchronous and continuous bouts of injury dysregulate the immune response to injured myofibers, exacerbating muscle degeneration and impairing regeneration. In contrast, activation of type 2 immunity during acute injury is required for efficient muscle regeneration. Evidence in the literature suggests a similar type 2 immune response is activated in dystrophic muscle, but is dysregulated by competing degenerative inflammatory responses. However, the regulation of type 2 immunity in dystrophic muscle is largely unknown. A recently identified subset of immune cells, group 2 innate lymphoid cells (ILC2), were shown to potently regulate type 2 immunity and promote tissue repair. In this study, we found that muscle ILC2s were increased in number and expressed higher levels of interleukin-5 (IL-5) in mdx mice compared to wildtype controls, indicating that muscle degeneration activates ILC2s. In vivo expansion of ILC2s using IL-2/anti-IL-2 complex (IL-2c) and IL-33 enhanced type 2 cytokine expression in mdx skeletal muscle and increased the cross-sectional area of regenerating myofibers, suggesting that ILC2s enhance muscle regeneration through the upregulation of type 2 cytokines. In addition, loss-and gain-of-function experiments demonstrated that ILC2s promote the skeletal muscle recruitment of eosinophils, an innate immune cell population previously shown to promote muscle regeneration. Collectively our data support a working model in which ILC2s promote skeletal muscle regeneration by enhancing type 2 immunity (i.e. eosinophilia and increased type 2 cytokines). |
| Databáze: | OpenAIRE |
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