Up-regulation of miR-618 suppresses the development of PDCs and increases their ability to secrete IFNα, potentially contributing to the type I IFN signature observed in SSc patients.
Genotype-mRNA expression correlation analysis revealed that the IRF8 protective allele was associated with increased interferon-gamma (IFN-γ) expression (P = 0.03) in patients with SSc but decreased type I IFN (IFIT1) expression in patients and controls (P = 0.02).
.To examine whether myxovirus-resistance protein A (MxA) mRNA expression, commonly considered a reliable marker of Type I interferon (IFN) bioactivity, is modified in patients with systemic sclerosis (SSc); if it is associated to specific clinical features; and if its modulation is accompanied by modulation of mRNA for the Type I IFN receptor (IFNAR).
Furthermore, plasma IFN-inducible chemokines correlate with the IFN gene expression score in SSc patients, enabling researchers to examine this molecular signature in large SSc cohorts with serum or plasma collection.
These findings indicate that rec gamma-IFN can modulate the excessive collagen biosynthesis characteristic of PSS fibroblasts and that this effect can be explained largely by the gamma-IFN-mediated decrease in specific collagen mRNAs.
A type I interferon (IFN) gene signature shared by systemic lupus erythematous (SLE) and systemic sclerosis (SSc) was used to evaluate an anti-type I IFN-α receptor (IFN-αR) monoclonal antibody, MEDI-546, in a phase I trial in SSc.
Taken together, these studies demonstrate an important role for type I IFN in skin fibrosis, and they provide a rationale for IFNAR1 inhibition in scleroderma.