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

Pöllinger, Bernadette, Junt, Tobias, Metzler, Barbara, Walker, Ulrich A, Tyndall, Alan, Allard, Cyril, Bay, Serkan, Keller, Roland, Raulf, Friedrich, Di Padova, Franco, O'Reilly, Terrence, Horwood, Nicole J ORCID: https://orcid.org/0000-0002-6344-1677, Patel, Dhavalkumar D and Littlewood-Evans, Amanda (2011) Th17 cells, not IL-17+ γδ T cells, drive arthritic bone destruction in mice and humans. Journal of Immunology, 186 (4). pp. 2602-2612. ISSN 0022-1767

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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.

Item Type:	Article
Uncontrolled Keywords:	adult,aged,animals,immunology,immunology,immunology,immunology,immunology,genetics,coculture techniques,administration & dosage,female,humans,biosynthesis,male,mice,mice, inbred dba,middle aged,immunology,biosynthesis,immunology
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	LivePure Connector
Date Deposited:	06 Mar 2019 10:30
Last Modified:	19 Oct 2023 02:23
URI:	https://ueaeprints.uea.ac.uk/id/eprint/70139
DOI:	10.4049/jimmunol.1003370

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