1. T Cell Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Juvenile Arthritis Is Contingent Upon Th17 Plasticity.
- Author
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Piper, Christopher, Pesenacker, Anne M., Bending, David, Thirugnanabalan, Balathas, Varsani, Hemlata, Wedderburn, Lucy R., and Nistala, Kiran
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T cells , *ACADEMIC medical centers , *ANALYSIS of variance , *CELL culture , *COLONY-stimulating factors (Physiology) , *STATISTICAL correlation , *FLOW cytometry , *INFLAMMATION , *POLYMERASE chain reaction , *RESEARCH funding , *JUVENILE idiopathic arthritis , *STATISTICS , *SYNOVIAL fluid , *DATA analysis , *REVERSE transcriptase polymerase chain reaction , *PHYSIOLOGY - Abstract
Objective. Granulocyte-macrophage colony stimulating factor (GM-CSF) is a potent inflammatory mediator that is responsible for recruitment and activation of innate immune cells. Recent data from murine studies have identified Th17 cells as a key source of GM-CSF and suggest that T cell-derived GM-CSF is instrumental in the induction of autoimmune disease. The present study was undertaken to analyze the expression of T cell-derived GM-CSF in the joints of patients with juvenile idiopathic arthritis (JIA) and to investigate the differentiation of Th17 cells and how this relates to GM-CSF+ T helper cells. Methods. Synovial fluid (SF) and peripheral blood (PB) samples from 24 patients with JIA were analyzed, by flow cytometry and reverse transcription-polymerase chain reaction, for expression of GM-CSF and the Th17 marker CD161. A cytokine capture assay was used to purify Th17 cells and test the plasticity of cytokine production in response to interleukin-12 (IL-12) and IL-23. Results. The frequency of GM-CSF-producing T helper cells was significantly enriched in SF mononuclear cells compared to PB mononuclear cells from the patients with JIA (24.1% of CD4+ T cells versus 2.9%) and closely correlated with the erythrocyte sedimentation rate (r2 = 0.91, P < 0.001). Synovial GMCSF + T cells were predominantly CD161+ and coexpressed interferon-γ (IFNγ), but not IL-17. Culture of Th17 cells in the presence of IL-12 led to rapid upregulation of GM-CSF and IFNγ, recapitulating the phenotype of GM-CSF-expressing cells within the joint. Conclusion. Our results identify a novel outcome of Th17 plasticity in humans that may account for the enrichment of GM-CSF-expressing T cells in the joints of patients with JIA. The association of GM-CSF expression with systemic inflammation highlights the potential role of Th17-related cytokines in the pathology of JIA. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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