@phdthesis{Sustal2020,
  author    = {Sustal, Klara Nela},
  title     = {T-Zell Hom{\"o}ostase und Plastizit{\"a}t in Juveniler idiopathischer Arthritis},
  doi       = {10.25972/OPUS-12386},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123863},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Juvenile idiopathic arthritis (JIA) is a chronic systemic inflammatory disease in childhood with unknown etiology. Previous studies have demonstrated an important role for CD4+ T helper cells. The aim of the present study was to investigate the T cell phenotype and cytokine profile in children with JIA with focus on disease activity. T cells from peripheral blood mononuclear cells of 84 children with JIA and 40 age-matched healthy donors (HD) were analyzed by flowcytometry. T cells from JIA patients were less differentiated with higher numbers of na{\"i}ve T cells compared to HD. Cytokine profile analysis revealed a reduced intracellular Th1- and Th2-specific cytokine production. Significantly higher levels of RORуt expression, the most important transcription factor of Th17 cells, were found during acute disease flare. Moreover, IL-17 production was significantly higher in patients with active disease compared to patients in remission. Furthermore, stimulation experiments with CCR6+CD4+ T cells, which we could identify as IL-17 producing cells, revealed distinct plasticity. Polarization of isolated CCR6+ cells into Th17, Th1 or regulatory T cells, respectively, was achieved using specific cytokines. Interestingly, the potential to polarize differed in JIA patients and healthy donors. T cells from JIA patients showed a more stable Th17 phenotype and restricted switching to Th1 or Treg. These results suggest a predominant Th17 phenotype of T cells in JIA patients. During disease flares, RORуt seems to be an important factor leading to Th17 polarization. An opposing modulation of Th1, Th2 or Treg was not found. In conclusion, a Th17 phenotype dominates during disease flares in JIA and underlines the role of inflammatory T cells in the etiopathogenesis of JIA. IL-17, CCR6 and RORуt, Th17-specific factors, may be interesting targets for novel therapeutic approaches in JIA.},
  subject      = {Juvenile chronische Arthritis},
  language  = {de}
}