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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2004 Nov;63(Suppl 2):ii92–ii95. doi: 10.1136/ard.2004.028332

Defining a role for fibroblasts in the persistence of chronic inflammatory joint disease

C Buckley, A Filer, O Haworth, G Parsonage, M Salmon
PMCID: PMC1766776  PMID: 15479882

Abstract

The most surprising feature of the inflammatory response in rheumatoid arthritis is not that it occurs but that it does not resolve. The persistence of the chronic inflammatory response in conjunction with ongoing joint destruction is an all too familiar finding in many patients with rheumatoid arthritis. Despite the use of effective anti-inflammatory agents and disease modifying drugs, a significant proportion of patients with rheumatoid arthritis continue to have resistant disease. Complete clinical remission is unusual for more than six months and a formal cure of the disease remains elusive. In this report we focus on how attempts to address the question of why rheumatoid arthritis persists have led to a different interpretation of the pathogenesis of rheumatoid disease; one in which alterations in stromal cells such as fibroblasts play an important role in the switch from resolving to persistent disease.

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Figure 1.

Figure 1

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 Leucocyte–stromal interactions are involved at every stage in the trafficking of leucocytes into, within, and out of tissues. The molecular basis by which leucocytes leave the circulation and migrate across endothelium has been well studied (step 1, endothelium). How leucocytes interact with stromal cells (step 2) and how they exit tissue into the lymphatics (step 3) remains poorly understood.

Figure 2.

Figure 2

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 Not all fibroblasts are the same. Fibroblasts from the rheumatoid, or normal synovium look different from fibroblasts from the skin and express different patterns of adhesion and matrix molecules compared with fibroblasts derived from the skin. Pictures (left) show fibroblasts labelled for fibronectin with nuclei counter stain. A range of markers (CD90, collagen III, CD44, VCAM-1 (CD106), CD40, and fibronectin) have been used to label either rheumatoid, normal synovium, or skin fibroblasts which have then been examined by flow cytometry.

Figure 3.

Figure 3

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 The dynamics of the synovial inflammatory infiltrate. The dynamic balance of cells in any tissue compartment depends on the balance of cells that enter, exit, proliferate, or die. Homoeostasis is maintained during normal inflammatory responses leading to resolution of the inflammatory infiltrate. In chronic persistent inflammation inappropriate accumulation of leucocytes is caused by stromal production of prosurvival (interferon ß) and proretentive (stromal cell derived factor 1 (SDF-1); CXCL12) factors by fibroblasts and other resident tissue stromal cells.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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