Association between IL-17 and IgA in the joints of patients with inflammatory arthropathies

BMC Immunol. 2017 Feb 6;18(1):8. doi: 10.1186/s12865-017-0189-9.

Abstract

Background: Hyperactive secretion and pathogenic effects of interleukin (IL)-17 and IgA have been detected in different arthropathies. Recent evidence has revealed that TH17 cytokines regulate mucosal IgA secretion. However, it is unknown whether and how IL-17 mediates synovial IgA production. Here we aim to investigate the connection of synovial IL-17 with IgA production in the joint. In this study we included synovial fluids (SF) from patients with rheumatoid arthritis (RA; n = 66), spondyloarthritis (SpA; n = 18) and osteoarthritis (OA; n = 36). The levels of IL-17, IL-6, transforming growth factor (TGF)-β1, B-cell-activating factor of the TNF family (BAFF) and anti-lipopolyssacharide (LPS) immunoglobulin (Ig)A were investigated by enzyme-linked immunosorbent assay (ELISA). Total IgA was measured by radial immunodiffusion assay. Synovial fluid-derived mononuclear cells (SFMC) were stimulated with bacterial antigens or SF-conditioned media, and cytokines and IgA were analyzed in the supernatants.

Results: IL-17, IL-6 and TGF-β1 were increased in SF from both RA and SpA compared with OA patients. Concentration of IL-17 correlated with the disease activity score (DAS)-28, IL-6 and anti-LPS IgA levels. Bacterial-stimulated SFMCs from RA and SpA patients secreted higher IL-17 than vehicle-stimulated SFMCs. Conditioned media with SF containing IL-17 induced anti-LPS IgA production by SFMCs which was independent of IL-6 activity. Concentrations of synovial TGF-β1 and BAFF correlated with anti-LPS and total IgA levels, respectively. Blockade of IL-17 decreased the production of TGF-β1 and anti-LPS IgA by SF-stimulated SFMCs.

Conclusions: This study reports a connection between IL-17 and IgA secretion in the joint. In addition, it demonstrates that enterobacterial antigens trigger synovial IL-17 production, and that TGF-β1 and BAFF may mediate the effect of IL-17 on IgA production. This circuit may contribute to the pathogenesis of inflammatory joint diseases.

Keywords: B-cell activating factor of the TNF family; Immunoglobulin A; Interleukin-17; Synovial fluid; Transforming growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B-Cell Activating Factor / metabolism
  • Child
  • Enterobacteriaceae Infections / immunology*
  • Female
  • Humans
  • Immunoglobulin A / metabolism
  • Inflammation / immunology*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Joints / immunology*
  • Male
  • Middle Aged
  • Spondylitis, Ankylosing / immunology*
  • Th17 Cells / immunology*
  • Transforming Growth Factor beta1 / immunology
  • Transforming Growth Factor beta1 / metabolism
  • Young Adult

Substances

  • B-Cell Activating Factor
  • Immunoglobulin A
  • Interleukin-17
  • TNFSF13B protein, human
  • Transforming Growth Factor beta1