Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis-prone HLA–B27–transgenic rats

✍ Scribed by Simon Glatigny; Ingrid Fert; Marie A. Blaton; Rik J. Lories; Luiza M. Araujo; Gilles Chiocchia; Maxime Breban

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 421 KB
• Volume: 64
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.33321

✦ Synopsis

Abstract

Objective

HLA–B27/human β~2~‐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.

Conclusion

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.