Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin‐15 on the cell surface and promote osteoclastogenesis in autologous monocytes

Miranda-Carús, María-Eugenia; Benito-Miguel, Marta; Balsa, Alejandro; Cobo‐Ibáñez, Tatiana; Ayala, Carlos Pérez de; Pascual‐Salcedo, Dora; Martı́n-Mola, Emilio

doi:10.1002/art.21731

Cited by 85 publications

(77 citation statements)

References 65 publications

(80 reference statements)

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“…Evidence of a direct role for T cells in mediating osteoclastogenesis is mixed (39)(40)(41). RANKL + CD4 + PB T cells isolated from patients with early RA, if cultured with monocytes for 2 wk at a high T cell:monocyte ratio (4:1), can induce osteoclast differentiation (41).…”

Section: Discussionmentioning

confidence: 99%

“…RANKL + CD4 + PB T cells isolated from patients with early RA, if cultured with monocytes for 2 wk at a high T cell:monocyte ratio (4:1), can induce osteoclast differentiation (41). Other studies have shown that activated PB T cells induce RANKL-dependent osteoclastogenesis from adherent PBMCs if these cultures are pretreated with M-CSF (40,42).…”

Section: Discussionmentioning

confidence: 99%

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Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis

Söderström

Stein

Colmenero

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

144

143

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Osteoclasts are bone-eroding cells that develop from monocytic precursor cells in the presence of receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Osteoclasts are essential for physiological bone remodeling, but localized excessive osteoclast activity is responsible for the periarticular bone destruction that characteristically occurs in patients with rheumatoid arthritis (RA). The origin of osteoclasts at sites of bone erosion in RA is unknown. Natural killer (NK) cells, as well as monocytes, are abundant in the inflamed joints of patients with RA. We show here that such NK cells express both RANKL and M-CSF and are frequently associated with CD14 + monocytes in the RA synovium. Moreover, when synovial NK cells are cocultured with monocytes in vitro, they trigger their differentiation into osteoclasts, a process dependent on RANKL and M-CSF. As in RA, NK cells in the joints of mice with collagen-induced arthritis (CIA) express RANKL. Depletion of NK cells from mice before the induction of CIA reduces the severity of subsequent arthritis and almost completely prevents bone erosion. These results suggest that NK cells may play an important role in the destruction of bone associated with inflammatory arthritis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis

Söderström

Stein

Colmenero

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

144

143

View full text Add to dashboard Cite

show abstract

“…Using RA synovial tissue fibroblasts, IL-17 enhanced IL-1-mediated IL-6 and CCL20 production (30,31) and the TNF-a-induced synthesis of IL-1b, IL-6, IL-8, and CCL20 (31,32), indicating that the effects of IL-17 may be caused by its ability to promote inflammation by inducing cytokines and chemokines (33,34). Furthermore, direct effector functions of Th17 cells in RA have been demonstrated in that receptor activator for NF-kB ligand (RANKL) expression on the surface of Th17 cells induces osteoclastogenesis (25,35,36), promoting cartilage and bone destruction independently of TNF-a and IL-1b (37,38). These proinflammatory cytokines induced by IL-17 might even feedback on the generation and expansion of further Th17 cells in this specific microenvironment of the joint.…”

Section: Cd4mentioning

confidence: 99%

Dopamine Induces IL-6–Dependent IL-17 Production via D1-Like Receptor on CD4 Naive T Cells and D1-Like Receptor Antagonist SCH-23390 Inhibits Cartilage Destruction in a Human Rheumatoid Arthritis/SCID Mouse Chimera Model

Nakano

Yamaoka

Hanami

et al. 2011

The Journal of Immunology

110

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A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1–D5. Several studies have shown that dopamine not only mediates interactions into the nervous system, but can contribute to the modulation of immunity via receptors expressed on immune cells. We have previously shown an autocrine/paracrine release of dopamine by dendritic cells (DCs) during Ag presentation to naive CD4+ T cells and found efficacious results of a D1-like receptor antagonist SCH-23390 in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis and in the NOD mouse model of type I diabetes, with inhibition of Th17 response. This study aimed to assess the role of dopaminergic signaling in Th17-mediated immune responses and in the pathogenesis of rheumatoid arthritis (RA). In human naive CD4+ T cells, dopamine increased IL-6–dependent IL-17 production via D1-like receptors, in response to anti-CD3 plus anti-CD28 mAb. Furthermore, dopamine was localized with DCs in the synovial tissue of RA patients and significantly increased in RA synovial fluid. In the RA synovial/SCID mouse chimera model, although a selective D2-like receptor antagonist haloperidol significantly induced accumulation of IL-6+ and IL-17+ T cells with exacerbated cartilage destruction, SCH-23390 strongly suppressed these responses. Taken together, these findings indicate that dopamine released by DCs induces IL-6–Th17 axis and causes aggravation of synovial inflammation of RA, which is the first time, to our knowledge, that actual evidence has shown the pathological relevance of dopaminergic signaling with RA.

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“…2 Although in physiological conditions RANKL is the main cytokine driving OC formation, and is principally expressed by mesenchymal cells of the osteoblast lineage, the osteoclastogenic cytokine is produced in abundance by T cells in states of destructive osteolytic bone disease associated with MM, as well as other pathologies with bone involvement. [3][4][5][6][7] It has long been recognized that infection, inflammation and auto-immune disorder are associated with systemic and local bone loss, [5][6][7] and recently several groups have shown a link between T cells and the development of osteolysis associated with malignancy. 3,4,8 Consistently, we showed earlier an important role of T cells in supporting the formation and survival of OCs in peripheral blood mononuclear cells (PBMCs) from MM patients with osteolysis.…”

Section: Introductionmentioning

confidence: 99%

Soluble decoy receptor 3 modulates the survival and formation of osteoclasts from multiple myeloma bone disease patients

et al. 2009

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Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor superfamily, is known to be involved in cell survival and osteoclast (OC) formation. In this study, we show that malignant plasma cells and T lymphocytes from multiple myeloma (MM) bone disease patients, as well as Karpas 909, a human myeloma cell line, directly produce DcR3. By interacting with FasL, this molecule could inhibit OC apoptosis. In fact, the use of a neutralizing anti-DcR3 antibody induces a reduction of cell viability with a consequent increase of apoptotic cell number, the activation of caspase-8 and -3, and DNA fragmentation. Furthermore, we show that DcR3 supports OC formation in samples from MM patients through the upregulation of RANKL and TNFa by T lymphocytes and only TNFa by CD14 þ cells. In conclusion, our data provide the first evidence of the expression of DcR3 in MM, and the involvement of this molecule in supporting the survival and formation of OCs from MM bone disease patients. The production of DcR3 by T lymphocytes confers these cells a role in the pathogenesis of bone disease associated with MM.

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Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin‐15 on the cell surface and promote osteoclastogenesis in autologous monocytes

Abstract: Objective. To investigate the osteoclastogenic potential of T cells from the peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) on autologous monocytes, and to study the cytokines implicated in this process. Methods. T cells and monocytes were isolated

Cited by 85 publications

References 65 publications

Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis

Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis

Dopamine Induces IL-6–Dependent IL-17 Production via D1-Like Receptor on CD4 Naive T Cells and D1-Like Receptor Antagonist SCH-23390 Inhibits Cartilage Destruction in a Human Rheumatoid Arthritis/SCID Mouse Chimera Model

Soluble decoy receptor 3 modulates the survival and formation of osteoclasts from multiple myeloma bone disease patients

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