Neutrophil Survival in Rheumatoid Arthritis
Author Information
Author(s): Greg Parsonage, Andew Filer, Magdalena Bik, Debbie Hardie, Sian Lax, Katherine Howlett, Leigh D Church, Karim Raza, See-Heng Wong, Emily Trebilcock, Dagmar Scheel-Toellner, Mike Salmon, Janet M Lord, Christopher D Buckley
Primary Institution: University of Birmingham
Hypothesis
Synovial fibroblasts bridge the biological responses that connect TH17 cells to neutrophils by producing neutrophil survival factors following their activation with IL-17.
Conclusion
The increased number of neutrophils with an extended lifespan found in the rheumatoid synovial microenvironment is partly accounted for by IL-17 and TNFα activation of synovial fibroblasts.
Supporting Evidence
- TH17-expressing CD4+ cells were found to accumulate within rheumatoid synovial tissue.
- RASF treated with IL-17 and TNFα effectively doubled the functional lifespan of neutrophils in coculture.
- Specific depletion of GM-CSF from RASFIL-17/TNF-conditioned medium demonstrated that this cytokine accounted for approximately one-half of the neutrophil survival activity.
Takeaway
In rheumatoid arthritis, certain immune cells help neutrophils live longer, which can make the inflammation worse.
Methodology
Neutrophils were cocultured with rheumatoid arthritis synovial fibroblasts treated with IL-17 and TNFα, and their survival was assessed using flow cytometry.
Potential Biases
Potential bias in patient selection and cytokine measurement methods.
Limitations
The study primarily focuses on in vitro findings, which may not fully replicate in vivo conditions.
Participant Demographics
Patients with rheumatoid arthritis undergoing joint replacement surgery, with a mix of genders and ages ranging from 30 to 77 years.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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