The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Cathepsin S activity regulates antigen presentation and immunity.
Open accessAbstract
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.
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Cited by
Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain
Clark, A. K., Yip, P. K., Grist, J., Gentry, C., Staniland, A. A., Marchand, F., Dehvari, M., Wotherspoon, G., Winter, J., Ullah, J., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610811104 · Cited by 489
Nakagawa, T. Y., Brissette, W. H., Lira, P. D., Griffiths, R. J., Petrushova, N., Stock, J., McNeish, J. D., Eastman, S. E., Howard, E. D., Clarke, S. R. M., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80021-7 · Cited by 416
Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment
Vidak, E., Javoršek, U., Vizovišek, M., & Turk, B. (2019) · Cells · doi:10.3390/cells8030264 · Cited by 398
Cathepsin K-Dependent Toll-Like Receptor 9 Signaling Revealed in Experimental Arthritis
Asagiri, M., Hirai, T., Kunigami, T., Kamano, S., Gober, H.-J., Okamoto, K., Nishikawa, K., Latz, E., Golenbock, D. T., Aoki, K., et al. (2008) · Science · doi:10.1126/science.1150110 · Cited by 364
Cathepsin cysteine proteases in cardiovascular disease
Lutgens, S. P. M., Cleutjens, K. B. J. M., Daemen, M. J. A. P., & Heeneman, S. (2007) · The FASEB Journal · doi:10.1096/fj.06-7924com · Cited by 351
Metadata
- Authors
- Riese, R. J., Mitchell, R. N., Villadangos, J. A., Shi, G. P., Palmer, J. T., Karp, E. R., De Sanctis, G. T., Ploegh, H. L., & Chapman, H. A.
- Venue
- Journal of Clinical Investigation
- Published
- 1998-06-01
- Volume
- 101
- Issue
- 11
- Pages
- 2351-2363
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1965771018
- Cited by
- 321
- References
- 49
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Riese, R. J., Mitchell, R. N., Villadangos, J. A., Shi, G. P., Palmer, J. T., Karp, E. R., De Sanctis, G. T., Ploegh, H. L., & Chapman, H. A. (1998). Cathepsin S activity regulates antigen presentation and immunity. Journal of Clinical Investigation. https://doi.org/10.1172/jci1158
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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