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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
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Citations to this article in year 2020 (10)

Title and authors Publication Year
Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics
R Brown, S Nath, A Lora, G Samaha, Z Elgamal, R Kaiser, C Taggart, S Weldon, P Geraghty
Respiratory Research 2020
Cathepsin S and Protease-Activated Receptor-2 Drive Alloimmunity and Immune Regulation in Kidney Allograft Rejection
Y Lei, B Ehle, SV Kumar, S Müller, S Moll, AF Malone, BD Humphreys, J Andrassy, HJ Anders
Frontiers in Cell and Developmental Biology 2020
Cathepsin S Regulates Antigen Processing and T Cell Activity in Non-Hodgkin Lymphoma
E Dheilly, E Battistello, N Katanayeva, S Sungalee, J Michaux, G Duns, S Wehrle, J Sordet-Dessimoz, M Mina, J Racle, P Farinha, G Coukos, D Gfeller, A Mottok, R Kridel, BE Correia, C Steidl, M Bassani-Sternberg, G Ciriello, V Zoete, E Oricchio
Cancer Cell 2020
Cathepsin S as a potential therapeutic target for chronic pain
K Montague-Cardoso, M Malcangio
2020
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PF Kuan, S Clouston, X Yang, R Kotov, E Bromet, BJ Luft
Translational Psychiatry 2020
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DB Singh, T Tripathi
2020
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
N Fuchs, M Meta, D Schuppan, L Nuhn, T Schirmeister
Cells 2020
Hepatic Stellate Cells and Hepatocytes as Liver Antigen-Presenting Cells during B. abortus Infection
PC Benitez, AI Viglietti, MM Elizalde, GH Giambartolomei, JF Quarleri, MV Delpino
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AK Edwards, KA Dunlap, TE Spencer, MC Satterfield
Genes & development 2020
A domain-based vaccine construct against SARS-CoV-2, the causative agent of COVID-19 pandemic: development of self-amplifying mRNA and peptide vaccines
MM Pourseif, S Parvizpour, B Jafari, J Dehghani, B Naghili, Y Omidi
Bioimpacts 2020

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