Fli1 Downregulation in Scleroderma Myeloid Cells Has Profibrotic and Proinflammatory Effects.

Frontiers in Immunology
Andreea M BujorMaria Trojanowska

Abstract

Scleroderma (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. We have previously demonstrated that low Fli1 expression in SSc fibroblasts and endothelial cells plays an important role in SSc pathogenesis. Cells of myeloid and lymphoid origin also express Fli1 and are dysregulated in patients with SSc, playing key roles in disease pathogenesis. However, the role for immune Fli1 in SSc is not yet clear. Our aim was to elucidate whether Fli1 contributes to the immune dysregulation seen in SSc. Comparison of the expression of Fli1 in monocytes, B- and T-cell fractions of PBMCs isolated from SSc patients and healthy controls (HC), showed an increase in Fli1 levels in monocytes. We used siRNA transfected human myeloid cells and mouse peritoneal macrophages obtained from Fli1 flox/flox LysMCre+/+ mice, and found that markers of alternative macrophage activation were increased with Fli1 deletion. Coculture of Fli1-deficient myeloid cells and primary human or mouse fibroblasts resulted in a potent induction of collagen type I, independent of TGFβ upregulation. We next analyzed global gene expression profile in response to Fli1 downregulation, to gain further insight into ...Continue Reading

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Datasets Mentioned

BETA
GSE144625

Methods Mentioned

BETA
biopsies
Transgenic
genotyping
lavage
PMA

Software Mentioned

GraphPad Prism
affy Bioconductor
Brainarray hugene20sthsentrezgcdf R
GraphPad Prims
R

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