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Citations to this article

Cathepsin S activity regulates antigen presentation and immunity.
R J Riese, … , H L Ploegh, H A Chapman
R J Riese, … , H L Ploegh, H A Chapman
Published June 1, 1998
Citation Information: J Clin Invest. 1998;101(11):2351-2363. https://doi.org/10.1172/JCI1158.
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Research Article Article has an altmetric score of 7

Cathepsin S activity regulates antigen presentation and immunity.

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Abstract

MHC class II molecules display antigenic peptides on cell surfaces for recognition by CD4(+) T cells. Proteolysis is required in this process both for degradation of invariant chain (Ii) from class II-Ii complexes to allow subsequent binding of peptides, and for generation of the antigenic peptides. The cysteine endoprotease, cathepsin S, mediates Ii degradation in human and mouse antigen-presenting cells. Studies described here examine the functional significance of cathepsin S inhibition on antigen presentation and immunity. Specific inhibition of cathepsin S in A20 cells markedly impaired presentation of an ovalbumin epitope by interfering with class II-peptide binding, not by obstructing generation of the antigen. Administration of a cathepsin S inhibitor to mice in vivo selectively inhibited activity of cathepsin S in splenocytes, resulting in accumulation of a class II-associated Ii breakdown product, attenuation of class II-peptide complex formation, and inhibition of antigen presentation. Mice treated with inhibitor had an attenuated antibody response when immunized with ovalbumin but not the T cell-independent antigen TNP-Ficoll. In a mouse model of pulmonary hypersensitivity, treatment with the inhibitor also abrogated a rise in IgE titers and profoundly blocked eosinophilic infiltration in the lung. Thus, inhibition of cathepsin S in vivo alters Ii processing, antigen presentation, and immunity. These data identify selective inhibition of cysteine proteases as a potential therapeutic strategy for asthma and autoimmune disease processes.

Authors

R J Riese, R N Mitchell, J A Villadangos, G P Shi, J T Palmer, E R Karp, G T De Sanctis, H L Ploegh, H A Chapman

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1991 Total
Citations: 3 5 5 11 12 10 4 9 19 7 10 6 11 2 18 8 8 16 12 7 9 10 12 12 7 13 13 1 1 261
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Y Qin, GP Shi
Pharmacology & Therapeutics 2011
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D Haves-Zburof, T Paperna, A Gour-Lavie, I Mandel, L Glass-Marmor, A Miller
Journal of Cellular and Molecular Medicine 2011
Cysteine Cathepsins: Markers and Therapy Targets in Lung Disorders
M Kasabova, A Saidi, C Naudin, J Sage, F Lecaille, G Lalmanach
Clinical Reviews in Bone and Mineral Metabolism 2011
Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity
M Baugh, D Black, P Westwood, E Kinghorn, K McGregor, J Bruin, W Hamilton, M Dempster, C Claxton, J Cai, J Bennett, C Long, H Mckinnon, P Vink, L Hoed, M Gorecka, K Vora, E Grant, MD Percival, AM Boots, MJ Lierop
Journal of Autoimmunity 2011
Lack of cathepsin activities alter or prevent the development of lung granulomas in a mouse model of sarcoidosis
AO Samokhin, JY Gauthier, MD Percival, D Brömme
Respiratory Research 2011
The Emerging Relevance of the Cysteine Protease Cathepsin S in Disease
DM Small, RE Burden, CJ Scott
Clinical Reviews in Bone and Mineral Metabolism 2011
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AK Clark, M Malcangio
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Annual Reports in Medicinal Chemistry
JJ Liu, TW Lee
Annual Reports in Medicinal Chemistry Volume 46 2011
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M Lemaire, S Deleu, ED Bruyne, EV Valckenborgh, E Menu, K Vanderkerken
Advances in Cancer Research Volume 110 2011
Human blood basophils do not act as antigen-presenting cells for the major birch pollen allergen Bet v 1
C Kitzmüller, B Nagl, S Deifl, C Walterskirchen, B Jahn-Schmid, GJ Zlabinger, B Bohle
Allergy 2011
Inhibition of Cathepsin S Reduces Allogeneic T Cell Priming but Not Graft-versus-Host Disease Against Minor Histocompatibility Antigens
H Fujii, SM Ivison, H Shimizu, R Kajiwara, A Kariminia, M Yan, JP Dutz, KR Schultz
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Identification of putative cathepsin S in mangrove red snapper Lutjanus argentimaculatus and its role in antigen presentation
J Zhou, L Li, ZH Cai
Developmental & Comparative Immunology 2011
Genetic and Pharmacological Evaluation of Cathepsin S in a Mouse Model of Asthma
K Deschamps, W Cromlish, S Weicker, S Lamontagne, SL Huszar, JY Gauthier, JS Mudgett, A Guimond, R Romand, N Frossard, MD Percival, D Slipetz, CM Tan
American journal of respiratory cell and molecular biology 2011
Intraperitoneal murine Echinococcus multilocularis infection induces differentiation of TGF-β-expressing DCs that remain immature: Immature dendritic cells in chronic alveolar echinococcosis
N Mejri, J Müller, B Gottstein
Parasite Immunology 2011
Cysteine Cathepsins and the Skeleton
D Brömme
Clinical Reviews in Bone and Mineral Metabolism 2011
Cathepsin S inhibitors: 2004 – 2010
A Lee-Dutra, DK Wiener, S Sun
Expert Opinion on Therapeutic Patents 2011
CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease
F Borghese, FI Clanchy
Expert Opinion on Therapeutic Targets 2011
Extracellular Matrix Degradation
WC Parks, RP Mecham
2011

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