title: T cell expression of granulocyte-macrophage colony-stimulating factor in juvenile arthritis is contingent upon Th17 plasticity.
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 (r(2) = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University College London, London, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Piper
authors.forename: Anne M
authors.initials: AM
authors.lastname: Pesenacker
authors.forename: David
authors.initials: D
authors.lastname: Bending
authors.forename: Balathas
authors.initials: B
authors.lastname: Thirugnanabalan
authors.forename: Hemlata
authors.initials: H
authors.lastname: Varsani
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: Kiran
authors.initials: K
authors.lastname: Nistala
mesh_terms: D001171:Arthritis, Juvenile / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008297:Male; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor