Dendritic cells in rheumatoid arthritis

Sarkar, Sujata; Fox, David A.

doi:10.2741/1560

Cited by 47 publications

(29 citation statements)

References 108 publications

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“…In both of these diseases of adults, the follicle-like structures in the lesions are populated with T cells, B cells, and FDCs similar to what we report here for children with newonset juvenile DM (43,44). The presence of dendritic cells in extranodal follicular structures in these 2 adult diseases has not been validated.…”

Section: Discussionmentioning

confidence: 56%

Extranodal lymphoid microstructures in inflamed muscle and disease severity of new‐onset juvenile dermatomyositis

Padilla¹,

Vallejo²,

Lacomis³

et al. 2009

Arthritis & Rheumatism

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Objective. Juvenile dermatomyositis (DM) is an autoimmune disease of childhood characterized by lesions in skin and muscle that are populated by plasmacytoid dendritic cells (PDCs) and lymphocyte infiltrates. We undertook this study to examine the cellular composition, organization, and molecular milieu of the cellular infiltrates in muscle in juvenile DM and to correlate the infiltrates with clinical disease manifestations.Methods. Since PDCs and lymphocyte foci express CCL19 and CCL21, we investigated for in situ formation of lymphoid microstructures that could be sites of extranodal immune activation.Results. Analyses of muscle biopsy samples from children with new-onset juvenile DM showed 3 categories of lesions: diffuse infiltrates, lymphocytic aggregates lacking follicle-like organization, and follicle-like structures. The last of these exhibited elements of classic lymphoid follicles, including networks of follicular dendritic cells and high endothelial venules. They also expressed high levels of CXCL13 and lymphotoxins known to support lymphoid organogenesis. There were also resident naive CD45RA؉ T cells and maternally derived B cells and PDCs. Patients with diffuse infiltrates or lymphocytic aggregates were responsive to standard therapy with steroids and methotrexate, but those with follicle-like structures tended to have severe disease that required additional agents such as intravenous Ig or rituximab.Conclusion. These data suggest that lymphoneogenesis is a component of the early disease process in juvenile DM. Ectopic lymphoid structures could indicate a severe course of disease; their early detection could be a tool for disease management.

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Section: Discussionmentioning

confidence: 56%

Extranodal lymphoid microstructures in inflamed muscle and disease severity of new‐onset juvenile dermatomyositis

Padilla¹,

Vallejo²,

Lacomis³

et al. 2009

Arthritis & Rheumatism

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“…The release of activin A by DCs may thus represent a strategy to counterbalance Th1-biased T cell polarization. Finally, activin A released during NK-DC interactions may contribute to the increased local and systemic levels of these cytokines detected in many acute and chronic inflammatory diseases, such as lichen planus or rheumatoid arthritis, characterized by the concomitant recruitment of these two cell types (20,(44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Activin A as a Mediator of NK–Dendritic Cell Functional Interactions

Seeger

Bosisio

Parolini

et al. 2014

The Journal of Immunology

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The interaction of NK cells with dendritic cells (DCs) results in reciprocal cell activation through the interaction of membrane proteins and the release of soluble factors. In this article, we report that in NK-DC cocultures, among a set of 84 cytokines investigated, activin A was the second highest induced gene, with CXCL8 being the most upregulated one. Activin A is a member of the TGF-beta superfamily and was previously shown to possess both proinflammatory and anti-inflammatory activities. In NK-DC cocultures, the induction of activin A required cell contact and was dependent on the presence of proinflammatory cytokines (i.e., IFN-gamma, TNF-alpha, and GM-CSF), as well as on NK cell-mediated DC killing. CD1(+) DCs were the main activin A producer cells among myeloid blood DC subsets. In NK-DC cocultures, inhibition of activin A by follistatin, a natural inhibitory protein, or by a specific blocking Ab, resulted in the upregulation of proinflammatory cytokine release (i.e., IL-6, IL-8, TNF-alpha) by DCs and in the increase of DC maturation. In conclusion, our study reports that activin A, produced during NK-DC interactions, represents a relevant negative feedback mechanism that might function to prevent excessive immune activation by DCs

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“…Attention, therefore, has been directed at possible roles of dendritic cells in initiation and perpetuation of rheumatoid synovitis (recently reviewed in Ref. [1]). Cells with dendritic morphology were initially recognized in RA synovial tissue over 2 decades ago.…”

Section: Interactions Between Synovial Dendritic and T Cellsmentioning

confidence: 99%

Synovial biology and T cells in rheumatoid arthritis

2005

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Events that occur in rheumatoid arthritis synovial tissues are responsible for the signs and symptoms of joint inflammation and for the eventual destruction of articular and periarticular structures that lead to joint dysfunction and disability. The three most abundant cell populations in RA synovium are synovial macrophages (type A synoviocytes), synovial fibroblasts (type B synoviocytes) and infiltrating T lymphocytes. Other important cell populations include B lymphocytes, dendritic cells, plasma cells, mast cells and osteoclasts. Our current understanding of rheumatoid arthritis is moving beyond previous concepts that view this disease as the consequence of a specific and focused humoral or cellular autoimmune response to a single autoantigen. Rather, a new view of rheumatoid arthritis is emerging, which seeks to understand this disease as the product of pathologic cell-cell interactions occurring within a unique and defined environment, the synovium. T lymphocytes in rheumatoid arthritis synovium interact closely with dendritic cells, the most potent antigen-presenting cell population in the immune system. T cells also interact with monocytes and macrophages and cytokine-activated T cells may be, especially, suited to trigger production of the important cytokine TNFα by synovial macrophages. Recent evidence also suggests a potent bidirectional interaction between synovial T cells and synovial fibroblasts, which can lead to activation of both cell types. An important role for synovial B lymphocytes has been emphasized recently, both by experimental data and by results of clinical interventions. B cells in synovium can interact with fibroblasts as well as with other cells of the immune system and their potential role as antigen-presenting cells in the joint is as yet underexplored. Rheumatoid arthritis synovium may be one of the most striking examples of pathologic, organ-specific interactions between immune system cells and resident tissue cell populations. This view of rheumatoid arthritis also leads to the prediction that novel approaches to treatment will more logically target the intercellular communication systems that maintain such interactions, rather than attempt to ablate a single cell population.

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Dendritic cells in rheumatoid arthritis

Cited by 47 publications

References 108 publications

Extranodal lymphoid microstructures in inflamed muscle and disease severity of new‐onset juvenile dermatomyositis

Extranodal lymphoid microstructures in inflamed muscle and disease severity of new‐onset juvenile dermatomyositis

Activin A as a Mediator of NK–Dendritic Cell Functional Interactions

Synovial biology and T cells in rheumatoid arthritis

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