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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/249632
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/249632
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str 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 Técnicas2025-10-22T11:30:06Zoai: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:34982025-10-22 11:30:06.95CONICET 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
_version_ 1846781891739385856
score 12.982451

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