Myogenic Progenitor Cells Exhibit Type I Interferon-Driven Proangiogenic Properties and Molecular Signature During Juvenile Dermatomyositis

被引：36

作者：

Gitiaux, Cyril ^{[1
,2
]}

Latroche, Claire ^{[2
]}

Weiss-Gayet, Michele ^{[3
]}

Rodero, Mathieu P. ^{[4
]}

Duffy, Darragh ^{[5
]}

Bader-Meunier, Brigitte ^{[6
]}

Glorion, Christophe ^{[7
]}

Nusbaum, Patrick ^{[8
]}

Bodemer, Christine ^{[9
]}

Mouchiroud, Guy ^{[3
]}

Chelly, Jamel ^{[2
]}

Germain, Stephane ^{[10
]}

Desguerre, Isabelle ^{[11
]}

Chazaud, Benedicte ^{[3
]}

机构：

[1] Univ Paris 05, Ctr Reference Malad Neuromusculaires, Dept Neurophysiol ClinAP HP,FILNEMUS, Hop Necker Enfants Malad,Garches Necker Mondor He, Paris, France

[2] Univ Paris 05, Inst Cochin, CNRS, INSERM,U1016,UMR 8104, Paris, France

[3] Univ Claude Bernard Lyon 1, Inst NeuroMyoGene, INSERM, CNRS,UMR 5310,U1217, Villeurbanne, France

[4] Inst Imagine, Lab Neurogenet & Neuroinflammat, INSERM, Paris, France

[5] Inst Pasteur, Immunobiol Dendrit Cells, INSERM, U1223, Paris, France

[6] Hop Necker Enfants Malad, Dept Rhumatol Pediat, AP HP, Paris, France

[7] Hop Necker Enfants Malad, Dept Chirurg Orthoped, AP HP, Paris, France

[8] Hop Cochin, Serv Biochim & Genet Mol, AP HP, Paris, France

[9] Hop Necker Enfants Malad, Dept Dermatol, AP HP, Paris, France

[10] PSL Res Univ, Coll France, CNRS, Ctr Interdisciplinary Res Biol,INSERM, Paris, France

[11] FILNEMUS, Ctr Reference Malad Neuromusculaires, Garches Necker Mondor Hendaye, AP HP, Paris, France

来源：

ARTHRITIS & RHEUMATOLOGY | 2018年 / 70卷 / 01期

关键词：

SKELETAL-MUSCLE REGENERATION; ENDOTHELIAL-CELLS; DISEASE-ACTIVITY; UP-REGULATION; ANGIOGENESIS; EXPRESSION; ASSOCIATION; ACTIVATION; CHEMOKINES; CHILDHOOD;

D O I：

10.1002/art.40328

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ObjectiveJuvenile 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 (MPCs) 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. MethodsHuman 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 MPCs. Histologic analysis of type I IFN in muscle biopsy samples was also performed. ResultsUsing human cell cocultures, we showed highly angiogenic properties of MPCs from JDM patients in association with the expression of an angiogenic molecular signature. Transcriptome analysis of MPCs freshly isolated from muscle samples revealed type I IFN as the master regulator of the most up-regulated genes in JDM-derived MPCs. Functionally, treatment of normal MPCs with type I IFN recapitulated the molecular pattern and the proangiogenic functions of JDM-derived MPCs. In vivo histologic investigation showed that MPCs synthesized type I IFN and major proangiogenic molecules in JDM muscle. Moreover, MPCs derived from JDM muscles that were characterized by strong vasculopathy produced higher levels of type I IFN, confirming MPCs as a cellular source of type I IFN during JDM, and this correlated with the severity of the disease. ConclusionThese results demonstrate a new type I IFN pathway in JDM that activates the production of angiogenic effectors by MPCs, triggering their proangiogenic function to promote vessel recovery and muscle reconstruction.

引用

页码：134 / 145

页数：12

共 51 条

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