Th17 lymphocyte-dependent degradation of joint cartilage by synovial fibroblasts in a humanized mouse model of arthritis and reversal by secukinumab.

European Journal of Immunology
Francesca MargheriMario Del Rosso

Abstract

How T-helper (Th) lymphocyte subpopulations identified in synovial fluid from patients with juvenile idiopathic arthritis (JIA) (Th17, classic Th1, or nonclassic Th1) drive joint damage is of great interest for the possible use of biological drugs that inhibit the specific cytokines. Our objective was to clarify the role of such Th subpopulations in the pathogenesis of articular cartilage destruction by synovial fibroblasts (SFbs), and the effect of Th17 blockage in an animal model. SFbs were isolated from healthy subjects and patients with JIA, and peripheral blood Th lymphocytes subsets were obtained from healthy subjects. Fragments of human cartilage from healthy subjects in a collagen matrix containing JIA or normal SFbs grafted underskin in SCID mice were used to measure cartilage degradation under the effects of Th supernatants. JIA SFbs overexpress MMP9 and MMP2 and Th17 induce both MMPs in normal SFbs, while nonclassic Th1 upregulate urokinase plasminogen activator (uPA) activity. In vitro invasive phenotype of normal SFbs is stimulated with conditioned medium of Th17 and nonclassic-Th1. In the in vivo "inverse wrap" model, normal SFbs stimulated with supernatants of Th17-lymphocytes and nonclassic Th1 produced a cartil...Continue Reading

References

Jan 1, 1994·Annual Review of Immunology·S Romagnani
Jun 18, 2002·Clinical & Experimental Metastasis·Mario Del RossoVincenzo Chiarugi
Sep 9, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Peter S BurrageConstance E Brinckerhoff
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kiran NistalaLucy R Wedderburn
Jun 21, 2011·Lancet·Berent PrakkenAlberto Martini
Dec 14, 2011·The New England Journal of Medicine·Iain B McInnes, Georg Schett
Sep 12, 2012·European Journal of Immunology·Laura MaggiFrancesco Annunziato
Sep 7, 2013·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Lorenzo CosmiFrancesco Annunziato
May 1, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Sabrina AmarGregg B Fields
Jul 30, 2017·Journal of Clinical Medicine·Motomu Hashimoto
Nov 2, 2017·Expert Opinion on Drug Discovery·Yue ZhongJin-Ao Duan
Dec 29, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kasper AlmholtPernille A Usher
Feb 9, 2018·Nature Reviews. Rheumatology·Joanna Collison
Jun 11, 2019·Autoimmunity Reviews·Francesca MargheriMario Del Rosso

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Citations

Jul 18, 2021·Pediatric Research·Alessio Mazzoni, Rolando Cimaz

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