Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors
- 13 November 2012
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Rheumatology
- Vol. 9 (1), 24-33
- https://doi.org/10.1038/nrrheum.2012.190
Abstract
Fibroblast-like synoviocytes (FLS) are cellular effectors of the inflammatory milieu that characterizes and precedes joint destruction in rheumatoid arthritis (RA). But what role do these cells have in creating the same environment to which they respond? Bottini and Firestein delve into the double life of FLS in RA pathogenesis. 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.Keywords
This publication has 87 references indexed in Scilit:
- Role of interferon regulatory factor 7 in serum‐transfer arthritis: Regulation of interferon‐β productionArthritis & Rheumatism, 2011
- JNK1, but Not JNK2, Is Required in Two Mechanistically Distinct Models of Inflammatory ArthritisThe American Journal of Pathology, 2011
- Suppression of collagen-induced arthritis in growth arrest and DNA damage-inducible protein 45β-deficient miceArthritis & Rheumatism, 2011
- Cadherin-11 regulates fibroblast inflammationProceedings of the National Academy of Sciences of the United States of America, 2011
- JNK-1 deficiency limits macrophage-mediated antigen-induced arthritisArthritis & Rheumatism, 2011
- Altered expression of microRNA‐203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activationArthritis & Rheumatism, 2010
- Synovial fibroblasts spread rheumatoid arthritis to unaffected jointsNature Medicine, 2009
- Gadd45β deficiency in rheumatoid arthritis: Enhanced synovitis through JNK signalingArthritis & Rheumatism, 2009
- Anti‐rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen‐induced arthritis in rodentsBritish Journal of Pharmacology, 2007
- Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblastsProceedings of the National Academy of Sciences of the United States of America, 2007