Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity
- Autores
- Vicente, Manuel M.; Alves, Inês; Fernandes, Ângela; Dias, Ana M.; Santos-Pereira, Beatriz; Elena Pérez-Anton; Sofia Santos; Yang, Tao; Correia, Alexandra; Münster-Kühnel, Anja; Almeida, Afonso R. M.; Ravens, Sarina; Rabinovich, Gabriel Adrián; Vilanova, Manuel; Sousa, Ana E.; Pinho, Salomé S.
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulateother thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycomecompositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the Nglycosylationprofile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showedremarkable defects in key developmental checkpoints, including ß-selection, regulatory T-cell generation and γδT-celldevelopment, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstratedthat a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. Inconclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated withi nflammation susceptibility.
Fil: Vicente, Manuel M.. Universidad de Porto; Portugal
Fil: Alves, Inês. Universidad de Porto; Portugal
Fil: Fernandes, Ângela. Universidad de Porto; Portugal
Fil: Dias, Ana M.. Universidad de Porto; Portugal
Fil: Santos-Pereira, Beatriz. Universidad de Porto; Portugal
Fil: Elena Pérez-Anton. Universidad de Porto; Portugal
Fil: Sofia Santos. Universidad de Porto; Portugal
Fil: Yang, Tao. Hannover Medical School. Institute of Immunology; Alemania
Fil: Correia, Alexandra. Universidad de Porto; Portugal
Fil: Münster-Kühnel, Anja. Hannover Medical School. Institute of Clinical Biochemistry; Alemania
Fil: Almeida, Afonso R. M.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal
Fil: Ravens, Sarina. Hannover Medical School. Institute of Immunology; Alemania
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vilanova, Manuel. Universidad de Porto; Portugal
Fil: Sousa, Ana E.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal
Fil: Pinho, Salomé S.. Universidad de Porto; Portugal - Materia
-
GLYCOSYLATION
THYMOCYTES
NEGATIVE SELECTION
GAMMA DELTA T CELLS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/249632
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3498 |
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CONICET Digital (CONICET) |
spelling |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversityVicente, Manuel M.Alves, InêsFernandes, ÂngelaDias, Ana M.Santos-Pereira, BeatrizElena Pérez-AntonSofia SantosYang, TaoCorreia, AlexandraMünster-Kühnel, AnjaAlmeida, Afonso R. M.Ravens, SarinaRabinovich, Gabriel AdriánVilanova, ManuelSousa, Ana E.Pinho, Salomé S.GLYCOSYLATIONTHYMOCYTESNEGATIVE SELECTIONGAMMA DELTA T CELLShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulateother thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycomecompositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the Nglycosylationprofile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showedremarkable defects in key developmental checkpoints, including ß-selection, regulatory T-cell generation and γδT-celldevelopment, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstratedthat a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. Inconclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated withi nflammation susceptibility.Fil: Vicente, Manuel M.. Universidad de Porto; PortugalFil: Alves, Inês. Universidad de Porto; PortugalFil: Fernandes, Ângela. Universidad de Porto; PortugalFil: Dias, Ana M.. Universidad de Porto; PortugalFil: Santos-Pereira, Beatriz. Universidad de Porto; PortugalFil: Elena Pérez-Anton. Universidad de Porto; PortugalFil: Sofia Santos. Universidad de Porto; PortugalFil: Yang, Tao. Hannover Medical School. Institute of Immunology; AlemaniaFil: Correia, Alexandra. Universidad de Porto; PortugalFil: Münster-Kühnel, Anja. Hannover Medical School. Institute of Clinical Biochemistry; AlemaniaFil: Almeida, Afonso R. M.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; PortugalFil: Ravens, Sarina. Hannover Medical School. Institute of Immunology; AlemaniaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vilanova, Manuel. Universidad de Porto; PortugalFil: Sousa, Ana E.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; PortugalFil: Pinho, Salomé S.. Universidad de Porto; PortugalSpringer2023-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/249632Vicente, Manuel M.; Alves, Inês; Fernandes, Ângela; Dias, Ana M.; Santos-Pereira, Beatriz; et al.; Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity; Springer; Cellular & Molecular Immunology; 20; 8; 6-2023; 955-9681672-7681CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41423-023-01052-7info:eu-repo/semantics/altIdentifier/doi/10.1038/s41423-023-01052-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:00:36Zoai:ri.conicet.gov.ar:11336/249632instacron: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:34982025-09-29 10:00:36.52CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity |
title |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity |
spellingShingle |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity Vicente, Manuel M. GLYCOSYLATION THYMOCYTES NEGATIVE SELECTION GAMMA DELTA T CELLS |
title_short |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity |
title_full |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity |
title_fullStr |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity |
title_full_unstemmed |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity |
title_sort |
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity |
dc.creator.none.fl_str_mv |
Vicente, Manuel M. Alves, Inês Fernandes, Ângela Dias, Ana M. Santos-Pereira, Beatriz Elena Pérez-Anton Sofia Santos Yang, Tao Correia, Alexandra Münster-Kühnel, Anja Almeida, Afonso R. M. Ravens, Sarina Rabinovich, Gabriel Adrián Vilanova, Manuel Sousa, Ana E. Pinho, Salomé S. |
author |
Vicente, Manuel M. |
author_facet |
Vicente, Manuel M. Alves, Inês Fernandes, Ângela Dias, Ana M. Santos-Pereira, Beatriz Elena Pérez-Anton Sofia Santos Yang, Tao Correia, Alexandra Münster-Kühnel, Anja Almeida, Afonso R. M. Ravens, Sarina Rabinovich, Gabriel Adrián Vilanova, Manuel Sousa, Ana E. Pinho, Salomé S. |
author_role |
author |
author2 |
Alves, Inês Fernandes, Ângela Dias, Ana M. Santos-Pereira, Beatriz Elena Pérez-Anton Sofia Santos Yang, Tao Correia, Alexandra Münster-Kühnel, Anja Almeida, Afonso R. M. Ravens, Sarina Rabinovich, Gabriel Adrián Vilanova, Manuel Sousa, Ana E. Pinho, Salomé S. |
author2_role |
author author author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
GLYCOSYLATION THYMOCYTES NEGATIVE SELECTION GAMMA DELTA T CELLS |
topic |
GLYCOSYLATION THYMOCYTES NEGATIVE SELECTION GAMMA DELTA T CELLS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulateother thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycomecompositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the Nglycosylationprofile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showedremarkable defects in key developmental checkpoints, including ß-selection, regulatory T-cell generation and γδT-celldevelopment, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstratedthat a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. Inconclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated withi nflammation susceptibility. Fil: Vicente, Manuel M.. Universidad de Porto; Portugal Fil: Alves, Inês. Universidad de Porto; Portugal Fil: Fernandes, Ângela. Universidad de Porto; Portugal Fil: Dias, Ana M.. Universidad de Porto; Portugal Fil: Santos-Pereira, Beatriz. Universidad de Porto; Portugal Fil: Elena Pérez-Anton. Universidad de Porto; Portugal Fil: Sofia Santos. Universidad de Porto; Portugal Fil: Yang, Tao. Hannover Medical School. Institute of Immunology; Alemania Fil: Correia, Alexandra. Universidad de Porto; Portugal Fil: Münster-Kühnel, Anja. Hannover Medical School. Institute of Clinical Biochemistry; Alemania Fil: Almeida, Afonso R. M.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal Fil: Ravens, Sarina. Hannover Medical School. Institute of Immunology; Alemania Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Vilanova, Manuel. Universidad de Porto; Portugal Fil: Sousa, Ana E.. Universidade Nova de Lisboa. Faculdade de Ciencias Medicas; Portugal Fil: Pinho, Salomé S.. Universidad de Porto; Portugal |
description |
T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens.Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulateother thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycomecompositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the Nglycosylationprofile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showedremarkable defects in key developmental checkpoints, including ß-selection, regulatory T-cell generation and γδT-celldevelopment, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstratedthat a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. Inconclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated withi nflammation susceptibility. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-06 |
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/11336/249632 Vicente, Manuel M.; Alves, Inês; Fernandes, Ângela; Dias, Ana M.; Santos-Pereira, Beatriz; et al.; Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity; Springer; Cellular & Molecular Immunology; 20; 8; 6-2023; 955-968 1672-7681 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/249632 |
identifier_str_mv |
Vicente, Manuel M.; Alves, Inês; Fernandes, Ângela; Dias, Ana M.; Santos-Pereira, Beatriz; et al.; Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity; Springer; Cellular & Molecular Immunology; 20; 8; 6-2023; 955-968 1672-7681 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://www.nature.com/articles/s41423-023-01052-7 info:eu-repo/semantics/altIdentifier/doi/10.1038/s41423-023-01052-7 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
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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1844613789260972032 |
score |
13.070432 |