Th17 cells, not IL-17+ γδ T cells, drive arthritic bone destruction in mice and humans

Bernadette Pöllinger, Tobias Junt, Barbara Metzler, Ulrich A Walker, Alan Tyndall, Cyril Allard, Serkan Bay, Roland Keller, Friedrich Raulf, Franco Di Padova, Terrence O'Reilly, Nicole J Horwood, Dhavalkumar D Patel, Amanda Littlewood-Evans

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

The mechanism whereby IL-17 drives rheumatoid arthritis remains incompletely understood. We demonstrate that anti-IL-17 therapy in collagen-induced arthritis ameliorates bone damage by reducing the number of osteoclasts in joints. We found equal numbers of CD4(+) Th17 and IL-17 producing γδ T cells in the joints of arthritic mice, and in vitro, both populations similarly induced osteoclastogenesis. However, individual depletion and adoptive transfer studies revealed that in vivo, Th17 cells dominated with regard to bone destruction. Unlike γδ T cells, Th17 cells were found in apposition to tartrate-resistant acid phosphatase positive osteoclasts in subchondral areas of inflamed joints, a pattern reproduced in patient biopsies. This localization was caused by Ag-specific retention, because OVA-primed Th17 cells showed a γδ T cell-like diffuse distribution. Because IL-23, as produced by osteoclasts, enhanced T cell-mediated osteoclastogenesis, we propose that Ag-specific juxtaposition is key to foster the molecular cross talk of Th17 cells and osteoclasts, thus driving arthritic bone destruction.

Original languageEnglish
Pages (from-to)2602-2612
Number of pages11
JournalJournal of Immunology
Volume186
Issue number4
Early online date2 Feb 2011
DOIs
Publication statusPublished - 15 Feb 2011

Keywords

  • Adult
  • Aged
  • Animals
  • Arthritis, Experimental/immunology
  • Arthritis, Rheumatoid/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • Cartilage, Articular/immunology
  • Cell Communication/immunology
  • Cell Differentiation/genetics
  • Coculture Techniques
  • Collagen Type II/administration & dosage
  • Female
  • Humans
  • Interleukin-17/biosynthesis
  • Male
  • Mice
  • Mice, Inbred DBA
  • Middle Aged
  • Osteoclasts/immunology
  • Receptors, Antigen, T-Cell, gamma-delta/biosynthesis
  • Th17 Cells/immunology

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