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While the underlying mechanism of capillary depletion remains uncertain, recent studies have identified an up\u2010regulation of type I interferon (IFN<\/jats:styled-content>) expression specific to JDM<\/jats:styled-content>. Given that myogenic precursor cells (MPC<\/jats:styled-content>s) exert proangiogenic activity during normal skeletal muscle regeneration, we hypothesized that they may also modulate vascular remodeling\/angiogenesis during JDM<\/jats:styled-content>. The aim of this study was to investigate that hypothesis.<\/jats:p><\/jats:sec>Methods<\/jats:title>Human cell cocultures were used to analyze angiogenic properties in patients with JDM<\/jats:styled-content>, patients with Duchenne's muscular dystrophy (DMD<\/jats:styled-content>) (control patients for vascular remodeling), and healthy control subjects. Transcriptome analysis was used to examine muscle\u2010derived MPC<\/jats:styled-content>s. Histologic analysis of type I IFN<\/jats:styled-content> in muscle biopsy samples was also performed.<\/jats:p><\/jats:sec>Results<\/jats:title>Using human cell cocultures, we showed highly angiogenic properties of MPC<\/jats:styled-content>s from JDM<\/jats:styled-content> patients in association with the expression of an angiogenic molecular signature. Transcriptome analysis of MPC<\/jats:styled-content>s freshly isolated from muscle samples revealed type I IFN<\/jats:styled-content> as the master regulator of the most up\u2010regulated genes in JDM<\/jats:styled-content>\u2010derived MPC<\/jats:styled-content>s. Functionally, treatment of normal MPC<\/jats:styled-content>s with type I IFN<\/jats:styled-content> recapitulated the molecular pattern and the proangiogenic functions of JDM<\/jats:styled-content>\u2010derived MPC<\/jats:styled-content>s. In vivo histologic investigation showed that MPC<\/jats:styled-content>s synthesized type I IFN<\/jats:styled-content> and major proangiogenic molecules in JDM<\/jats:styled-content> muscle. Moreover, MPC<\/jats:styled-content>s derived from JDM<\/jats:styled-content> muscles that were characterized by strong vasculopathy produced higher levels of type I IFN<\/jats:styled-content>, confirming MPC<\/jats:styled-content>s as a cellular source of type I IFN<\/jats:styled-content> during JDM<\/jats:styled-content>, and this correlated with the severity of the disease.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>These results demonstrate a new type I IFN<\/jats:styled-content> pathway in JDM<\/jats:styled-content> that activates the production of angiogenic effectors by MPC<\/jats:styled-content>s, triggering their proangiogenic function to promote vessel recovery and muscle reconstruction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40328","type":"journal-article","created":{"date-parts":[[2017,9,21]],"date-time":"2017-09-21T10:42:49Z","timestamp":1505990569000},"page":"134-145","source":"Crossref","is-referenced-by-count":50,"title":["Myogenic Progenitor Cells Exhibit Type I 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