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

Autores
Scholand, Kaitlin K.; Galletti, Jeremías Gastón; Haap, Wolfgang; Santos Ferreira, Tiago; Ullmer, Christoph; de Paiva, Cintia S.
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: CD25KO 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.Methods: 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.Results: 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.Conclusions: Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.
Fil: Scholand, Kaitlin K.. Baylor College of Medicine; Estados Unidos. Rice University; Estados Unidos
Fil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Haap, Wolfgang. F. Hoffmann-La Roche; Suiza
Fil: Santos Ferreira, Tiago. F. Hoffmann-La Roche; Suiza
Fil: Ullmer, Christoph. F. Hoffmann-La Roche; Suiza
Fil: de Paiva, Cintia S.. Baylor College of Medicine; Estados Unidos. Rice University; Estados Unidos
Materia
DRY EYE
CATHEPSIN S
LACRIMAL GLAND
OCULAR SURFACE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266866
Acceder
id CONICETDig_3d12d1c7fa50d9006f2a20bd440c82d3
oai_identifier_str oai:ri.conicet.gov.ar:11336/266866
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland PathologyScholand, Kaitlin K.Galletti, Jeremías GastónHaap, WolfgangSantos Ferreira, TiagoUllmer, Christophde Paiva, Cintia S.DRY EYECATHEPSIN SLACRIMAL GLANDOCULAR SURFACEhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Purpose: CD25KO 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.Methods: 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.Results: 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.Conclusions: Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.Fil: Scholand, Kaitlin K.. Baylor College of Medicine; Estados Unidos. Rice University; Estados UnidosFil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Haap, Wolfgang. F. Hoffmann-La Roche; SuizaFil: Santos Ferreira, Tiago. F. Hoffmann-La Roche; SuizaFil: Ullmer, Christoph. F. Hoffmann-La Roche; SuizaFil: de Paiva, Cintia S.. Baylor College of Medicine; Estados Unidos. Rice University; Estados UnidosAssociation for Research in Vision & Ophthalmology2024-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266866Scholand, Kaitlin K.; Galletti, Jeremías Gastón; Haap, Wolfgang; Santos Ferreira, Tiago; Ullmer, Christoph; et al.; Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology; Association for Research in Vision & Ophthalmology; Investigative Ophthalmology & Visual Science; 65; 8; 7-2024; 1-111552-5783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2800434info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.65.8.26info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:56:16Zoai:ri.conicet.gov.ar:11336/266866instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:56:16.64CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
title Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
spellingShingle Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
Scholand, Kaitlin K.
DRY EYE
CATHEPSIN S
LACRIMAL GLAND
OCULAR SURFACE
title_short Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
title_full Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
title_fullStr Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
title_full_unstemmed Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
title_sort Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology
dc.creator.none.fl_str_mv Scholand, Kaitlin K.
Galletti, Jeremías Gastón
Haap, Wolfgang
Santos Ferreira, Tiago
Ullmer, Christoph
de Paiva, Cintia S.
author Scholand, Kaitlin K.
author_facet Scholand, Kaitlin K.
Galletti, Jeremías Gastón
Haap, Wolfgang
Santos Ferreira, Tiago
Ullmer, Christoph
de Paiva, Cintia S.
author_role author
author2 Galletti, Jeremías Gastón
Haap, Wolfgang
Santos Ferreira, Tiago
Ullmer, Christoph
de Paiva, Cintia S.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv DRY EYE
CATHEPSIN S
LACRIMAL GLAND
OCULAR SURFACE
topic DRY EYE
CATHEPSIN S
LACRIMAL GLAND
OCULAR SURFACE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: CD25KO 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.Methods: 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.Results: 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.Conclusions: Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.
Fil: Scholand, Kaitlin K.. Baylor College of Medicine; Estados Unidos. Rice University; Estados Unidos
Fil: Galletti, Jeremías Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Haap, Wolfgang. F. Hoffmann-La Roche; Suiza
Fil: Santos Ferreira, Tiago. F. Hoffmann-La Roche; Suiza
Fil: Ullmer, Christoph. F. Hoffmann-La Roche; Suiza
Fil: de Paiva, Cintia S.. Baylor College of Medicine; Estados Unidos. Rice University; Estados Unidos
description Purpose: CD25KO 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.Methods: 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.Results: 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.Conclusions: Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.
publishDate 2024
dc.date.none.fl_str_mv 2024-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266866
Scholand, Kaitlin K.; Galletti, Jeremías Gastón; Haap, Wolfgang; Santos Ferreira, Tiago; Ullmer, Christoph; et al.; Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology; Association for Research in Vision & Ophthalmology; Investigative Ophthalmology & Visual Science; 65; 8; 7-2024; 1-11
1552-5783
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266866
identifier_str_mv Scholand, Kaitlin K.; Galletti, Jeremías Gastón; Haap, Wolfgang; Santos Ferreira, Tiago; Ullmer, Christoph; et al.; Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease–Like Lacrimal Gland Pathology; Association for Research in Vision & Ophthalmology; Investigative Ophthalmology & Visual Science; 65; 8; 7-2024; 1-11
1552-5783
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2800434
info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.65.8.26
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Association for Research in Vision & Ophthalmology
publisher.none.fl_str_mv Association for Research in Vision & Ophthalmology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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