Document Detail


Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors.
MedLine Citation:
PMID:  23147896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nunzio Bottini; Gary S Firestein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-11-13
Journal Detail:
Title:  Nature reviews. Rheumatology     Volume:  9     ISSN:  1759-4804     ISO Abbreviation:  Nat Rev Rheumatol     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-24     Completed Date:  2013-05-28     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  101500080     Medline TA:  Nat Rev Rheumatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  24-33     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Arthritis, Rheumatoid / immunology,  metabolism,  pathology*
Cell Movement
Fibroblasts / immunology,  metabolism,  pathology*
Humans
Hyperplasia
Immunologic Factors / metabolism
Phenotype
Synovial Membrane / immunology,  metabolism,  pathology*
Grant Support
ID/Acronym/Agency:
R01 AI067752/AI/NIAID NIH HHS; R01 AI070555/AI/NIAID NIH HHS; R01 AI070555/AI/NIAID NIH HHS; R01 AR047825/AR/NIAMS NIH HHS; R01 AR47825/AR/NIAMS NIH HHS; R01AI067752/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Immunologic Factors
Comments/Corrections

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