@article{NosterdeKoningMaieretal.2016,
  author    = {Noster, Rebecca and de Koning, Heleen D. and Maier, Elisabeth and Prelog, Martina and Lainka, Elke and Zielinski, Christina E.},
  title     = {Dysregulation of proinflammatory versus anti-inflammatory human T\(_H\)17 cell functionalities in the autoinflammatory Schnitzler syndrome},
  series = {Journal of Allergy and Clinical Immunology},
  volume    = {138},
  journal   = {Journal of Allergy and Clinical Immunology},
  number    = {4},
  doi       = {10.1016/j.jaci.2015.12.1338},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187205},
  pages     = {1161-1169.e6},
  year      = {2016},
  abstract  = {Background: T\(_H\)17 cells have so far been considered to be crucial mediators of autoimmune inflammation. Two distinct types of T\(_H\)17 cells have been described recently, which differed in their polarization requirement for IL-1b and in their cytokine repertoire. Whether these distinct T\(_H\)17 phenotypes translate into distinct T\(_H\)17 cell functions with implications for human health or disease has not been addressed yet. Objective: We hypothesized the existence of proinflammatory and anti-inflammatory human T\(_H\)17 cell functions based on the differential expression of IL-10, which is regulated by IL-1 beta. Considering the crucial role of IL-1 beta in the pathogenesis of autoinflammatory syndromes, we hypothesized that IL-1 beta mediates the loss of anti-inflammatory T\(_H\)17 cell functionalities in patients with Schnitzler syndrome, an autoinflammatory disease. Methods: To assess proinflammatory versus anti-inflammatory T\(_H\)17 cell functions, we performed suppression assays and tested the effects of IL-1 beta dependent and independent T\(_H\)17 subsets on modulating proinflammatory cytokine secretion by monocytes. Patients with Schnitzler syndrome were analyzed for changes in T\(_H\)17 cell functions before and during therapy with IL-1 beta-blocking drugs. Results: Both T\(_H\)17 cell subsets differ in their ability to suppress T-cell proliferation and their ability to modulate proinflammatory cytokine production by antigen-presenting cells because of their differential IL-10 expression properties. In patients with Schnitzler syndrome, systemic overproduction of IL-1 beta translates into a profound loss of anti-inflammatory T\(_H\)17 cell functionalities, which can be reversed by anti-IL-1b treatment. Conclusion: IL-1 beta signaling determines the differential expression pattern of IL-10, which is necessary and sufficient to induce proinflammatory versus anti-inflammatory T\(_H\)17 cell functions. Our data introduce T\(_H\)17 cell subsets as novel players in autoinflammation and thus novel therapeutic targets in autoinflammatory syndromes including other IL-1 beta mediated diseases. This demonstrates for the first time alterations in the adaptive immune system in patients with autoinflammatory syndromes.},
  language  = {en}
}