Prolonged, granulocyte–macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha

Parsonage, Greg; Filer, Andrew; Bik, Magdalena; Hardie, Debbie L.; Lax, Siân; Howlett, Katherine; Church, Leigh D; Raza, Karim; Wong, See-Heng; Trebilcock, Emily; Scheel‐Toellner, Dagmar; Salmon, Mike; Lord, Janet M.; Buckley, Christopher D.

doi:10.1186/ar2406

Cited by 81 publications

(62 citation statements)

References 30 publications

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“…IL17 is a critical cytokine for protection of mucosal sites against extracellular bacteria. It stimulates production of neutrophil chemokines and neutrophil growth and survival factors such as G-CSF and GM-CSF and production of anti-microbial peptides by epithelial cells, both of which are critical for clearance of extracellular bacteria [38, 39]. Individuals with a genetic deficiency in IL17 components exhibit increased S .…”

Section: Discussionmentioning

confidence: 99%

A Neonatal Murine Model of MRSA Pneumonia

et al. 2017

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Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality in infants particularly following lower respiratory tract viral infections such as Respiratory Syncytial Virus (RSV). However, the mechanisms by which co-infection of infants by MRSA and RSV cause increased lung pathology are unknown. Because the infant immune system is qualitatively and quantitatively different from adults we developed a model of infant MRSA pneumonia which will allow us to investigate the effects of RSV co-infection on disease severity. We infected neonatal and adult mice with increasing doses of MRSA and demonstrate that neonatal mice have delayed kinetics in clearing the bacteria in comparison to adult mice. There were differences in recruitment of immune cells into the lung following infection. Adult mice exhibited an increase in neutrophil recruitment that coincided with reduced bacterial titers followed by an increase in macrophages. Neonatal mice, however, exhibited an early increase in neutrophils that did not persist despite continued presence of the bacteria. Unlike the adult mice, neonatal mice failed to exhibit an increase in macrophages. Neonates exhibited a decrease in phagocytosis of MRSA suggesting that the decrease in clearance was partially due to deficient phagocytosis of the bacteria. Both neonates and adults responded with an increase in pro-inflammatory cytokines following infection. However, in contrast to the adult mice, neonates did not express constitutive levels of the anti-microbial peptide Reg3γ in the lung. Infection of neonates did not stimulate expression of the co-stimulatory molecule CD86 by dendritic cells and neonates exhibited a diminished T cell response compared to adult mice. Overall, we have developed a neonatal model of MRSA pneumonia that displays a similar delay in bacterial clearance as is observed in the neonatal intensive care unit and will be useful for performing co-infection studies.

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Section: Discussionmentioning

confidence: 99%

A Neonatal Murine Model of MRSA Pneumonia

et al. 2017

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“…Mouse models have suggested a critical role of IL-17A in RA since IL-17A deficiency or antagonism has profound antiarthritic effects (2,3). Data coming from human in vitro experiments demonstrated their effects on joint degradation through the induction of RANKL, metalloproteinases (4 -6), and neutrophil survival, in part through GM-CSF (7).…”

Section: R Heumatoid Arthritis (Ra)mentioning

confidence: 99%

Genome-Wide Comparison between IL-17A- and IL-17F-Induced Effects in Human Rheumatoid Arthritis Synoviocytes

Zrioual

Écochard

Tournadre

et al. 2009

The Journal of Immunology

157

158

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IL-17A is implicated in rheumatoid arthritis (RA) pathogenesis; however, the contribution of IL-17F remains to be clarified. Using microarrays and gene-specific expression assays, we compared the regulatory effects of IL-17A and IL-17F alone or in combination with TNF-α on RA synoviocytes. IL-17A and IL-17F expression was studied in osteoarthritis and RA synovium by immunohistochemistry. The comparison between the IL-17A and IL-17F stimulatory effect on RA synoviocytes was assessed at the protein level by ELISA and at the mRNA level by microarrays and real-time RT-PCR. TNFRII expression was studied by real-time RT-PCR and immunofluorescence, and neutralizing Ab was used to analyze its contribution to CCL20 secretion. IL-17A and IL-17F were detected in plasma cell-like cells from RA but not osteoarthritis synovium. In microarrays, IL-17A and IL-17F alone had similar regulatory effects, IL-17F being quantitatively less active. Both cytokines induced a similar expression pattern in the presence of TNF-α. Based on a cooperation index, 130 and 203 genes were synergistically induced by IL-17A or IL-17F plus TNF-α, respectively. Among these, the new target genes CXCR4, LPL, and IL-32 were validated by real-time RT-PCR. IL-17A and IL-17F up-regulated TNFRII expression, but had no effects on TNFRI, IL-17RA or IL-17RC. TNFRII blockade inhibited the synergistic induction of CCL20 by IL-17A or IL-17F and TNF-α. IL-17A and IL-17F are both expressed in RA synovium. In the presence of TNF-α, they induced a similar expression pattern in RA synoviocytes. Accordingly, IL-17F appears as a target in Th17-mediated diseases such as RA.

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“…Indeed, following stimulation by IL-17, RA fibroblast-like synovial cells upregulate the chemotactic factors IL-8, Gro-α, and Gro-β [70]. After pretreatment of RA synovial fibroblasts with IL-17 and TNF, subsequent co-culture of these cells with neutrophils effectively doubled neutrophil lifespan through the inhibition of apoptotic pathways [71]. Additionally, IL-17 has been linked to the upregulation of IL-16, a chemoattractant cytokine for CD4 + monocytes, and monocyte-chemoattractant protein-1 (MCP-1), and thus may also be involved in the influx of inflammatory macrophages in the synovium [72–74].…”

Section: Mechanisms Of Il-17 Driven Joint Destructionmentioning

confidence: 99%

Breaking old paradigms: Th17 cells in autoimmune arthritis

Peck

Mellins

2009

Clinical Immunology

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Aberrant helper T cell activation has been implicated in the pathogenesis of an array of autoimmune diseases. In this review, we summarize evidence that suggests the involvement of a novel T cell subset, the Th17 lineage, in rheumatoid arthritis. In particular, we focus on the role of Th17 cells in inducing and perpetuating the chronic inflammation, cartilage damage, and bone erosion that are hallmark phases of joint destruction and consider current and emerging therapies that seek to disrupt the inflammatory Th17 network and shift the immune system back towards homeostasis.

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Prolonged, granulocyte–macrophage colony-stimulating factor-dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha

Cited by 81 publications

References 30 publications

A Neonatal Murine Model of MRSA Pneumonia

A Neonatal Murine Model of MRSA Pneumonia

Genome-Wide Comparison between IL-17A- and IL-17F-Induced Effects in Human Rheumatoid Arthritis Synoviocytes

Breaking old paradigms: Th17 cells in autoimmune arthritis

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