The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis

Abstract

An IFN type I signature is observed in patients with SSc from the earliest phases of the disease, even before overt skin fibrosis. The presence of IFN type I signature in monocytes is correlated with BAFF mRNA expression and serum PIIINP levels, supporting a contribution in the pathogenesis and progression of SSc.

Association of MicroRNA‐618 Expression With Altered Frequency and Activation of Plasmacytoid Dendritic Cells in Patients With Systemic Sclerosis

“…Macrophages and DCs from IRF-8-deficient mice remain immature and have impaired responses to TLR activation. It is possible that the up-regulated expression of miR-618 in PDCs from SSc patients also results in increased IFNa release in vivo, thus contributing to the establishment of the type I IFN signature observed in SSc patients (14,35,52). This is the first study to demonstrate that the silencing of IRF-8 impairs the activation of primary human PDCs, resulting in decreased IFNa secretion by PDCs.…”

Contribution of Interleukin-6 to the Pathogenesis of Systemic Sclerosis

“…B cell activating factor (BAFF) is a cytokine thatisprimarilyproducedbymonocytes,macrophages,and myofibroblasts and is implicated in the regulation of B cell survival,activation,proliferation,andmaturation (77). Serum levelsofBAFFwereelevatedinpatientswithSScandcorrelatedwiththeextentofskinfibrosisinSSc (78).Moreover,it wasreportedthatBAFFmRNAlevelsinmonocytesinpatients with SSc, especially in IFN type I signature positive monocytes (79).BAFFreceptor(BAFFR)wasalsooverexpressedin BcellsofpatientswithSSc (80).Thoseobservationssuggest that the signal transduction through BAFF/BAFFR may contribute to the activation of B cells in SSc. The activation of B cells is one of the key pathways to induce excessive IL-6 productioninSSc.…”

Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics

“…pDCs infiltrate the skin early during development of psoriasis, and can initiate psoriasis in an IFN-α-dependent manner in a mouse xenograft model (100). The blood of a subset of patients with systemic sclerosis also exhibits an IFN signature (101, 102), which is especially prominent during the earliest disease phases, even before overt skin fibrosis (103). Finally, transient increased expression of type I IFN signature is found during preclinical T1D and is a risk factor for autoimmunity in children with genetic predisposition to the disease (104).…”