Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors
By N. Bottini, Gary S. Firestein. Nature Reviews Rheumatology, 2012
867 citations recorded by the source corpus.
Rheumatoid arthritis (RA) is characterized by hyperplastic synovial pannus tissue, which mediates destruction of cartilage and bone. Fibroblast-like synoviocytes (FLS) are a key component of this invasive synovium and have a major role in the initiation and perpetuation of destructive joint inflammation. The pathogenic potential of FLS in RA stems from their ability to express immunomodulating cytokines and mediators as well as a wide array of adhesion molecule and matrix-modelling enzymes. FLS can be viewed as 'passive responders' to the immunoreactive process in RA, their activated phenotype reflecting the proinflammatory milieu. However, FLS from patients with RA also display unique aggressive features that are autonomous and vertically transmitted, and these cells can behave as primary promoters of inflammation. The molecular bases of this 'imprinted aggressor' phenotype are being clarified through genetic and epigenetic studies. The dual behaviour of FLS in RA suggests that FLS-directed therapies could become a complementary approach to immune-directed therapies in this disease. Pathophysiological characteristics of FLS in RA, as well as progress in targeting these cells, are reviewed in this manuscript.
Subfields: Immunology, Pulmonary and Respiratory Medicine, Rheumatology
View Paper: https://www.semanticscholar.org/paper/d12578d34edc280883a5b08927444c3aaa236ee9
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Citations in the corpus
- Immunopathogenesis of rheumatoid arthritis (2017, neutral): “…implicated, including abnormal DNA methylation (see below), somatic mutations in various genes (e.g., p53, mitochondria, vimentin), defective PTEN expression, and high levels of sentrin (Pap et al., 2000; Franz et al., 2000; Firestein et al., 1997; and reviewed in Bottini and Firestein, 2013b).”
- Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “Cell-specific cytokines, include TNF-α, IL-1, and IL-6 from macrophages, IL-6, IL-7, and IL-15 from memory T-cells, IL-1 and IL-17 from helper T-cells, and IL-1, IL-6, IL-18, GM-CSF, and TGF-β from synovial fibroblasts (303, 308).”