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Myogenic Progenitor Cells Exhibit Type I Interferon–Driven Proangiogenic Properties and Molecular Signature During Juvenile Dermatomyositis
Author(s) -
Gitiaux Cyril,
Latroche Claire,
WeissGayet Michèle,
Rodero Mathieu P.,
Duffy Darragh,
BaderMeunier Brigitte,
Glorion Christophe,
Nusbaum Patrick,
Bodemer Christine,
Mouchiroud Guy,
Chelly Jamel,
Germain Stéphane,
Desguerre Isabelle,
Chazaud Bénédicte
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40328
Subject(s) - juvenile dermatomyositis , angiogenesis , myogenesis , dermatomyositis , medicine , skeletal muscle , interferon , progenitor cell , transcriptome , duchenne muscular dystrophy , pathology , cancer research , biology , immunology , stem cell , microbiology and biotechnology , gene expression , gene , biochemistry
Objective Juvenile dermatomyositis ( JDM ) is an inflammatory pediatric myopathy characterized by focal capillary loss in muscle, followed by progressive recovery upon adequate treatment with immunomodulating drugs, although some patients remain refractory to treatment. While the underlying mechanism of capillary depletion remains uncertain, recent studies have identified an up‐regulation of type I interferon ( IFN ) expression specific to JDM . Given that myogenic precursor cells ( MPC s) exert proangiogenic activity during normal skeletal muscle regeneration, we hypothesized that they may also modulate vascular remodeling/angiogenesis during JDM . The aim of this study was to investigate that hypothesis. Methods Human cell cocultures were used to analyze angiogenic properties in patients with JDM , patients with Duchenne's muscular dystrophy ( DMD ) (control patients for vascular remodeling), and healthy control subjects. Transcriptome analysis was used to examine muscle‐derived MPC s. Histologic analysis of type I IFN in muscle biopsy samples was also performed. Results Using human cell cocultures, we showed highly angiogenic properties of MPC s from JDM patients in association with the expression of an angiogenic molecular signature. Transcriptome analysis of MPC s freshly isolated from muscle samples revealed type I IFN as the master regulator of the most up‐regulated genes in JDM ‐derived MPC s. Functionally, treatment of normal MPC s with type I IFN recapitulated the molecular pattern and the proangiogenic functions of JDM ‐derived MPC s. In vivo histologic investigation showed that MPC s synthesized type I IFN and major proangiogenic molecules in JDM muscle. Moreover, MPC s derived from JDM muscles that were characterized by strong vasculopathy produced higher levels of type I IFN , confirming MPC s as a cellular source of type I IFN during JDM , and this correlated with the severity of the disease. Conclusion These results demonstrate a new type I IFN pathway in JDM that activates the production of angiogenic effectors by MPC s, triggering their proangiogenic function to promote vessel recovery and muscle reconstruction.