title: Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis-prone HLA-B27-transgenic rats.
abstract: OBJECTIVE
  HLA-B27/human β2-microglobulin-transgenic (B27-transgenic) rats, a model of spondylarthritis (SpA), develop spontaneous colitis and arthritis under conventional conditions. CD4+ T cells are pivotal in the development of inflammation in B27-transgenic rats. This study was undertaken to characterize the phenotype of CD4+ T cells in this model and to determine whether dendritic cells (DCs) induce proinflammatory T cells.
  
  
  METHODS
  The phenotype of CD4+ T cells from rat lymph nodes (LNs) draining the sites of inflammation was analyzed by flow cytometry. Immunostaining was used to detect interleukin-17 (IL-17)-producing cells in the rat joints. DCs from B27-transgenic or control rats (transgenic for HLA-B7 or nontransgenic) were cocultured with control CD4+ T cells and stimulated with anti-T cell receptor α/β.
  
  
  RESULTS
  IL-17A- and tumor necrosis factor α (TNFα)-producing CD4+ T cells were expanded in mesenteric and popliteal LNs from B27-transgenic rats. The accumulation of Th17 cells correlated with disease development, in contrast to Th1 or Treg cells. IL-17-positive mononuclear cells were detected in the arthritic joints of B27-transgenic rats but not in the joints of control rats. Finally, in vitro cocultures demonstrated that Th17 cells were preferentially induced and expanded by DCs from B27-transgenic rats, by a process that may involve defective engagement of costimulatory molecules.
  
  
  CONCLUSIONS
  Our findings indicate that expanded CD4+ T cells in B27-transgenic rats exhibit a proinflammatory Th17 phenotype characterized by IL-17A and TNFα production. Furthermore, this population is preferentially induced by DCs from B27-transgenic rats. These data point toward an induction of Th17 cells as a possible pathogenic mechanism in this model of SpA. However, their pathogenic role still needs to be shown.
authors: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), and INSERM U1016, Paris, France.
authors: Simon
authors: S
authors: Glatigny
authors: Ingrid
authors: I
authors: Fert
authors: Marie A
authors: MA
authors: Blaton
authors: Rik J
authors: RJ
authors: Lories
authors: Luiza M
authors: LM
authors: Araujo
authors: Gilles
authors: G
authors: Chiocchia
authors: Maxime
authors: M
authors: Breban
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology*; D007596:Joints / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D025241:Spondylarthritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin