CCL20 produced in the cytokine network of rheumatoid arthritis recruits CCR6+ mononuclear cells and enhances the production of IL-6

Cytokine. 2009 Aug;47(2):112-8. doi: 10.1016/j.cyto.2009.05.009. Epub 2009 Jun 16.

Abstract

Although a notable amount of CCL20 is detectable in the synovial fluid of human rheumatoid arthritis (RA), its role in the pathogenesis of RA remains to be determined. IL-1beta vigorously induced the production of CCL20 from FLSs of human RA and the production of CCL20 induced by TNF-alpha was partially attributed to a trace amount of IL-1beta induced by TNF-alpha. Although IL-6 failed to induce CCL20, TNF-alpha-induced IL-6 enhanced the production of CCL20 in an autocrine/paracrine manner. To determine the role of CCL20 and its sole receptor CCR6 in the recruitment of mononuclear cells (MNCs) into the inflamed joint of RA, conditioned medium of IL-1beta-stimulated FLSs was used in migration assays. The conditioned medium significantly recruited CCR6(+) MNCs in a CCL20-dependent manner. The production of CCL20 induced by TNF-alpha and IL-1beta was modified by helper-T-cell-derived cytokines. Interestingly, CCL20 enhanced the production of IL-6 coordinately with the stimulation of IL-17 but not with that of IFN-gamma. These findings imply FLSs stimulated by proinflammatory cytokines recruit CCR6(+) MNCs including IL-17-producing-helper T cells into the inflamed joint, leading to the enhancement of the production of CCL20, which chemokine and IL-17 coordinately induce proinflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Cells, Cultured
  • Chemokine CCL20 / biosynthesis*
  • Chemotaxis, Leukocyte*
  • Cytokines / pharmacology*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-17 / pharmacology
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / pharmacology
  • Leukocytes, Mononuclear / immunology
  • Receptors, CCR6 / analysis*
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • CCR6 protein, human
  • Chemokine CCL20
  • Cytokines
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-6
  • Receptors, CCR6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma