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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.

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

02/2011

Volume

186

Pages

2602 - 2612

Addresses

Department of Autoimmunity, Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.

Keywords

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