Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology

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dc.citation.articleNumber26
dc.citation.issueNumber8
dc.citation.journalTitleInvestigative Ophthalmology & Visual Science
dc.citation.volumeNumber65
dc.contributor.authorScholand, Kaitlin K.
dc.contributor.authorGalletti, Jeremias
dc.contributor.authorHaap, Wolfgang
dc.contributor.authorSantos-Ferreira, Tiago
dc.contributor.authorUllmer, Christoph
dc.contributor.authorde Paiva, Cintia S.
dc.date.accessioned2024-08-09T16:25:25Z
dc.date.available2024-08-09T16:25:25Z
dc.date.issued2024
dc.description.abstractCD25KO mice are a model of Sjögren disease (SjD) driven by autoreactive T cells. Cathepsin S (CTSS) is a protease crucial for major histocompatibility complex class II presentation that primes T cells. We investigated if a diet containing CTSS inhibitor would improve autoimmune signs in CD25KO mice. Four-week female CD25KO mice were randomly chosen to receive chow containing a CTSS inhibitor (R05461111, 262.5 mg/kg chow) or standard chow for 4 weeks. Cornea sensitivity was measured. Inflammatory score was assessed in lacrimal gland (LG) histologic sections. Flow cytometry of LG and ocular draining lymph nodes (dLNs) investigated expression of Th1 and Th17 cells. Expression of inflammatory, T- and B-cell, and apoptotic markers in the LG were assessed with quantitative PCR. The life span of mice receiving CTSS inhibitor or standard chow was compared. CD4+ T cells from both groups were isolated from spleens and adoptively transferred into RAG1KO female recipients. Mice receiving CTSS inhibitor had better cornea sensitivity and improved LG inflammatory scores. There was a significant decrease in the frequency of CD4+ immune cells and a significant increase in the frequency of CD8+ immune cells in the dLNs of CTSS inhibitor mice. There was a significant decrease in Th1 and Th17 cells in CTSS inhibitor mice in both LGs and dLNs. Ifng, Ciita, and Casp8 mRNA in CTSS inhibitor mice decreased. Mice that received the CTSS inhibitor lived 30% longer. Adoptive transfer recipients with CTSS inhibitor-treated CD4+ T cells had improved cornea sensitivity and lower inflammation scores. Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.
dc.identifier.citationScholand, K. K., Galletti, J., Haap, W., Santos-Ferreira, T., Ullmer, C., & de Paiva, C. S. (2024). Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology. Investigative Ophthalmology & Visual Science, 65(8), 26. https://doi.org/10.1167/iovs.65.8.26
dc.identifier.digitali1552-5783-65-8-26_1721126025-71969
dc.identifier.doihttps://doi.org/10.1167/iovs.65.8.26
dc.identifier.urihttps://hdl.handle.net/1911/117635
dc.language.isoeng
dc.publisherARVO
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleInhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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