IL-17 induces monocyte migration in rheumatoid arthritis

J Immunol. 2009 Mar 15;182(6):3884-91. doi: 10.4049/jimmunol.0802246.

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease which is in part mediated by the migration of monocytes from blood to RA synovial tissue, where they differentiate into macrophages and secrete inflammatory cytokines and chemokines. The T cell cytokine IL-17 is expressed in the RA synovial tissue and synovial fluid. To better understand the mechanism by which IL-17 might promote inflammation, its role in monocyte trafficking was examined. In vivo, IL-17 mediates monocyte migration into sponges implanted into SCID mice. In vitro, IL-17 was chemotactic, not chemokinetic, for monocytes at the concentrations detected in the RA synovial fluid. Further, IL-17-induced monocyte migration was mediated by ligation to IL-17RA and RC expressed on monocytes and was mediated through p38MAPK signaling. Finally, neutralization of IL-17 in RA synovial fluid or its receptors on monocytes significantly reduced monocyte migration mediated by RA synovial fluid. These observations suggest that IL-17 may be important in recruiting monocytes into the joints of patients with RA, supporting IL-17 as a therapeutic target in RA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • Chemotaxis, Leukocyte / immunology*
  • Female
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / physiology
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / physiology*
  • MAP Kinase Signaling System / immunology
  • Mice
  • Mice, SCID
  • Monocytes / enzymology
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Synovial Membrane / enzymology
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / physiology

Substances

  • Inflammation Mediators
  • Interleukin-17
  • p38 Mitogen-Activated Protein Kinases