BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands

Alsaleh, Ghada; Messer, Laurent; Semaan, Noha; Boulanger, Nathalie; Gottenberg, Jacques-Éric; Sibilia, Jean; Wachsmann, Dominique

doi:10.1002/art.22915

Cited by 34 publications

(30 citation statements)

References 41 publications

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“…High levels of both BAFF and APRIL, along with their receptors, are found in the rheumatoid synovium [15] with APRIL being produced by synovial DCs and BAFF by tissue macrophages [18] and synovial fibroblasts. Both cytokines are also produced by synovial B cells [67,68]. Using human synovium-severe combined immunodeficiency (SCID) synovial grafts, Seyler et al demonstrated that BAFF/APRIL blockade destroys the FDC network within ectopic germinal centres which then decrease in size.…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

BAFF: a local and systemic target in autoimmune diseases

Moisini

Davidson

2009

Clinical and Experimental Immunology

156

141

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Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

BAFF: a local and systemic target in autoimmune diseases

Moisini

Davidson

2009

Clinical and Experimental Immunology

156

141

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“…BAFF has been demonstrated to be produced not only by inflammatory cells but also by RA-FLS [54] following treatment with IFNgamma or TNFalpha [55]. Although the question of what cytokines can stimulate RA-FLS to synthesize BAFF de novo cannot be answered, other findings have shown that engagement of alpha5beta1 integrins on RA-FLS induces the expression of BAFF in these cells [56]. These data strengthen the aforementioned link between fibroblast attachment to cartilage components such as fibronectin and their specific activation in RA.…”

Section: Ra-fls Contribute To the Accumulation Of Infiltrating T-and mentioning

confidence: 99%

Cell death in rheumatoid arthritis

2009

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Apoptosis plays a pivotal role in tissue homoeostasis both under physiological and pathological conditions and several studies have shown that some characteristic changes in the composition and structure of the inflamed synovial membrane in rheumatoid arthritis (RA) are linked to an altered apoptotic response of synovial cells. As a result, a hyperplastic synovial tissue is generated that mediates the progressive destruction of articular cartilage and bone. In addition to inflammatory cells, these changes most prominently affect resident fibroblast-like cells that have been demonstrated to be of utmost importance for joint destruction. Once activated, these cells pass through prominent molecular changes resulting in an aggressive, invasive behaviour. Research of the past years has identified different mechanisms that prevent synovial cells in RA from apoptosis. They include changes in the mitochondrial pathway as well as altered expression of downstream modulators of death receptors and transcriptional regulators such as NFkappaB. This review summarises our recent progress in understanding aberrant apoptosis in the RA synovial membrane and points to possibilities of intervening specifically with this aspect of the pathogenesis of RA.

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“…Doreau et al [77] also found that IL-17A and BAFF induced expression of MEF2C, which is an important mediator of BCR-induced proliferation [90]. Importantly, IL-17A and BAFF expression are regulated by TNF [91][92][93][94] and TWIST1 is over-expressed in the synovium of patients with RA [95].…”

Section: Il-17 Blockadementioning

confidence: 97%

The effect of targeted rheumatoid arthritis therapies on anti-citrullinated protein autoantibody levels and B cell responses

Modi

Soejima

Levesque

2013

Clinical and Experimental Immunology

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SummaryRheumatoid arthritis (RA) is a complex inflammatory disorder associated with synovitis and joint destruction that affects an estimated 1·3 million Americans and causes significant morbidity, a reduced life-span and lost work productivity. The use of biological therapies for the treatment of RA is costly, and the selection of therapies is still largely empirical and not guided by the underlying biological features of the disease in individual patients. The synovitis associated with RA is characterized by an influx of B and T cells, macrophages and neutrophils and the expansion of fibroblast-like synoviocytes, which form pannus and lead to cartilage and bone destruction. RA is associated with synovial production of rheumatoid factor (RF) and anticitrullinated protein autoantibodies (ACPA) and with the production of inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-17 and tumour necrosis factor (TNF)-a, which are targets for RA therapeutics. Recent ideas about the pathogenesis of RA emphasize a genetic predisposition to develop RA, a preclinical phase of disease that is associated with the production of ACPA and the development of symptomatic disease following inflammatory initiating events that are associated with expression of citrullinated epitopes in the joints of patients. However, we still have a limited understanding of the cytokine and intracellular pathways that regulate ACPA levels. In humans, therapy with biological agents affords a unique opportunity to better understand the cytokine and signalling pathways regulating ACPA levels and the impact of ACPA level changes on disease activity. In this study we summarize the effect of RA therapies on ACPA levels and B cell responses.

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BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands

Cited by 34 publications

References 41 publications

BAFF: a local and systemic target in autoimmune diseases

BAFF: a local and systemic target in autoimmune diseases

Cell death in rheumatoid arthritis

The effect of targeted rheumatoid arthritis therapies on anti-citrullinated protein autoantibody levels and B cell responses

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