Brief Report: T Cell Expression of Granulocyte–Macrophage Colony‐Stimulating Factor in Juvenile Arthritis Is Contingent Upon Th17 Plasticity. Issue 7 (July 2014) - Piper, Christopher
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 GM‐CSF+ 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 up‐regulation 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.