Myogenic Progenitor Cells Exhibit Type I Interferon-Driven Proangiogenic Properties and Molecular Signature During Juvenile Dermatomyositis - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Arthritis & rheumatology Année : 2018

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

Claire Latroche
  • Fonction : Auteur
Darragh Duffy
Christine Bodemer
Jamel Chelly
  • Fonction : Auteur
  • PersonId : 899153

Résumé

OBJECTIVE: Juvenile DermatoMyositis (JDM) is an inflammatory pediatric myopathy characterized by focal capillary loss in muscle, followed by a progressive recovery upon adequate immunomodulating treatments, although some patients remain refractory to treatments. While the underlying mechanism of capillary depletion remains uncertain, recent studies have identified an upregulation of type I Interferon (IFN-I) expression specific to JDM. Given that myogenic precursor cells (MPCs) exert pro-angiogenic activity during normal skeletal muscle regeneration, we hypothesized that they may also modulate vascular remodeling /angiogenesis during JDM. METHODS AND RESULTS: Using human cell cocultures, we showed that the high angiogenic properties of MPCs of JDM patients, associated with the expression of an angiogenic molecular signature. Moreover, transcriptomic analysis of MPCs freshly isolated from patient muscle identified IFN-I as the master regulator of the most upregulated genes in JDM-derived MPCs. Functionally, treatment of normal MPCs with IFN-I recapitulated the molecular pattern and the pro-angiogenic functions of JDM-derived MPCs. In vivo histological investigation showed that MPCs synthesized IFN-I and major pro-angiogenic molecules in JDM muscle. Moreover, MPCs that derived from JDM muscles characterized by a strong vasculopathy, produced higher levels of IFN-I, confirming MPCs as a cellular source of IFN-I during JDM, that correlated with the severity of the disease. CONCLUSION: These results demonstrate a new IFN-I pathway in JDM, which activates the production of angiogenic effectors by MPCs, triggering their pro-angiogenic function to promote vessel recovery and muscle reconstruction.

Domaines

Immunologie

Dates et versions

pasteur-01620313 , version 1 (31-05-2022)

Identifiants

Citer

Cyril Gitiaux, Claire Latroche, Michèle Weiss-Gayet, Mathieu P Rodero, Darragh Duffy, et al.. Myogenic Progenitor Cells Exhibit Type I Interferon-Driven Proangiogenic Properties and Molecular Signature During Juvenile Dermatomyositis. Arthritis & rheumatology, 2018, 70 (1), pp.134-145. ⟨10.1002/art.40328⟩. ⟨pasteur-01620313⟩
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