Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation

Autores
Segovia, M.; Louvet, C.; Charnet, P.; Savina, A.; Tilly, G.; Gautreau, L.; Carretero-Iglesia, L.; Beriou, G.; Cebrián, José Ignacio; Cens, T.; Hepburn, L.; Chiffoleau, E.; Floto, R. A.; Anegon, I.; Amigorena, S.; Hill, M.; Cuturi, M. C.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8(+) CD11c(+) T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b(-/-) ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b(-/-) ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8(+) T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8(+) CD11c(+) T cells with regulatory properties and prolong graft survival.
Fil: Segovia, M.. Center for Research inTransplantation and Immunology; Francia
Fil: Louvet, C.. Center for Research inTransplantation and Immunology; Francia
Fil: Charnet, P.. Centre de Recherche en Biologie cellulaire de Montpellier; Francia
Fil: Savina, A.. Institut Curie; Francia. INSERM; Francia
Fil: Tilly, G.. Center for Research inTransplantation and Immunology; Francia
Fil: Gautreau, L.. Center for Research inTransplantation and Immunology; Francia
Fil: Carretero-Iglesia, L.. Center for Research inTransplantation and Immunology; Francia
Fil: Beriou, G.. Center for Research inTransplantation and Immunology; Francia
Fil: Cebrián, José Ignacio. Institut Curie, Inserm U932, Immunité Et Cancer; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Cens, T.. Centre de Recherche en Biologie cellulaire de Montpellier; Francia
Fil: Hepburn, L.. University of Cambridge. Cambridge Institute for Medical Research, Department of Medicine, ; Reino Unido
Fil: Chiffoleau, E.. Center for Research inTransplantation and Immunology; Francia
Fil: Floto, R. A.. University of Cambridge. Cambridge Institute for Medical Research, Department of Medicine, ; Reino Unido. Center for Research inTransplantation and Immunology; Francia
Fil: Anegon, I.. Center for Research inTransplantation and Immunology; Francia
Fil: Amigorena, S.. Institut Curie; Francia. INSERM; Francia
Fil: Hill, M.. Center for Research inTransplantation and Immunology; Francia
Fil: Cuturi, M. C.. Center for Research inTransplantation and Immunology; Francia
Materia
Autologous Dendritic Cells
Cellular Therapy
Cross-Presentation
Ion Channel
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/31016
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/31016
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentationSegovia, M.Louvet, C.Charnet, P.Savina, A.Tilly, G.Gautreau, L.Carretero-Iglesia, L.Beriou, G.Cebrián, José IgnacioCens, T.Hepburn, L.Chiffoleau, E.Floto, R. A.Anegon, I.Amigorena, S.Hill, M.Cuturi, M. C.Autologous Dendritic CellsCellular TherapyCross-PresentationIon Channelhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8(+) CD11c(+) T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b(-/-) ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b(-/-) ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8(+) T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8(+) CD11c(+) T cells with regulatory properties and prolong graft survival.Fil: Segovia, M.. Center for Research inTransplantation and Immunology; FranciaFil: Louvet, C.. Center for Research inTransplantation and Immunology; FranciaFil: Charnet, P.. Centre de Recherche en Biologie cellulaire de Montpellier; FranciaFil: Savina, A.. Institut Curie; Francia. INSERM; FranciaFil: Tilly, G.. Center for Research inTransplantation and Immunology; FranciaFil: Gautreau, L.. Center for Research inTransplantation and Immunology; FranciaFil: Carretero-Iglesia, L.. Center for Research inTransplantation and Immunology; FranciaFil: Beriou, G.. Center for Research inTransplantation and Immunology; FranciaFil: Cebrián, José Ignacio. Institut Curie, Inserm U932, Immunité Et Cancer; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Cens, T.. Centre de Recherche en Biologie cellulaire de Montpellier; FranciaFil: Hepburn, L.. University of Cambridge. Cambridge Institute for Medical Research, Department of Medicine, ; Reino UnidoFil: Chiffoleau, E.. Center for Research inTransplantation and Immunology; FranciaFil: Floto, R. A.. University of Cambridge. Cambridge Institute for Medical Research, Department of Medicine, ; Reino Unido. Center for Research inTransplantation and Immunology; FranciaFil: Anegon, I.. Center for Research inTransplantation and Immunology; FranciaFil: Amigorena, S.. Institut Curie; Francia. INSERM; FranciaFil: Hill, M.. Center for Research inTransplantation and Immunology; FranciaFil: Cuturi, M. C.. Center for Research inTransplantation and Immunology; FranciaWiley Blackwell Publishing, Inc2014-04-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31016Cuturi, M. C.; Hill, M.; Amigorena, S.; Anegon, I.; Floto, R. A.; Chiffoleau, E.; et al.; Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation; Wiley Blackwell Publishing, Inc; American Journal of Transplantation; 14; 14-4-2014; 1021-10311600-6135CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com.gate2.inist.fr/doi/10.1111/ajt.12708/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/ajt.12708info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:08Zoai:ri.conicet.gov.ar:11336/31016instacron: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:34982025-09-03 09:48:08.655CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
title Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
spellingShingle Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
Segovia, M.
Autologous Dendritic Cells
Cellular Therapy
Cross-Presentation
Ion Channel
title_short Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
title_full Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
title_fullStr Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
title_full_unstemmed Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
title_sort Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation
dc.creator.none.fl_str_mv Segovia, M.
Louvet, C.
Charnet, P.
Savina, A.
Tilly, G.
Gautreau, L.
Carretero-Iglesia, L.
Beriou, G.
Cebrián, José Ignacio
Cens, T.
Hepburn, L.
Chiffoleau, E.
Floto, R. A.
Anegon, I.
Amigorena, S.
Hill, M.
Cuturi, M. C.
author Segovia, M.
author_facet Segovia, M.
Louvet, C.
Charnet, P.
Savina, A.
Tilly, G.
Gautreau, L.
Carretero-Iglesia, L.
Beriou, G.
Cebrián, José Ignacio
Cens, T.
Hepburn, L.
Chiffoleau, E.
Floto, R. A.
Anegon, I.
Amigorena, S.
Hill, M.
Cuturi, M. C.
author_role author
author2 Louvet, C.
Charnet, P.
Savina, A.
Tilly, G.
Gautreau, L.
Carretero-Iglesia, L.
Beriou, G.
Cebrián, José Ignacio
Cens, T.
Hepburn, L.
Chiffoleau, E.
Floto, R. A.
Anegon, I.
Amigorena, S.
Hill, M.
Cuturi, M. C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autologous Dendritic Cells
Cellular Therapy
Cross-Presentation
Ion Channel
topic Autologous Dendritic Cells
Cellular Therapy
Cross-Presentation
Ion Channel
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8(+) CD11c(+) T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b(-/-) ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b(-/-) ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8(+) T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8(+) CD11c(+) T cells with regulatory properties and prolong graft survival.
Fil: Segovia, M.. Center for Research inTransplantation and Immunology; Francia
Fil: Louvet, C.. Center for Research inTransplantation and Immunology; Francia
Fil: Charnet, P.. Centre de Recherche en Biologie cellulaire de Montpellier; Francia
Fil: Savina, A.. Institut Curie; Francia. INSERM; Francia
Fil: Tilly, G.. Center for Research inTransplantation and Immunology; Francia
Fil: Gautreau, L.. Center for Research inTransplantation and Immunology; Francia
Fil: Carretero-Iglesia, L.. Center for Research inTransplantation and Immunology; Francia
Fil: Beriou, G.. Center for Research inTransplantation and Immunology; Francia
Fil: Cebrián, José Ignacio. Institut Curie, Inserm U932, Immunité Et Cancer; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Cens, T.. Centre de Recherche en Biologie cellulaire de Montpellier; Francia
Fil: Hepburn, L.. University of Cambridge. Cambridge Institute for Medical Research, Department of Medicine, ; Reino Unido
Fil: Chiffoleau, E.. Center for Research inTransplantation and Immunology; Francia
Fil: Floto, R. A.. University of Cambridge. Cambridge Institute for Medical Research, Department of Medicine, ; Reino Unido. Center for Research inTransplantation and Immunology; Francia
Fil: Anegon, I.. Center for Research inTransplantation and Immunology; Francia
Fil: Amigorena, S.. Institut Curie; Francia. INSERM; Francia
Fil: Hill, M.. Center for Research inTransplantation and Immunology; Francia
Fil: Cuturi, M. C.. Center for Research inTransplantation and Immunology; Francia
description The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8(+) CD11c(+) T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b(-/-) ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b(-/-) ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8(+) T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8(+) CD11c(+) T cells with regulatory properties and prolong graft survival.
publishDate 2014
dc.date.none.fl_str_mv 2014-04-14
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/11336/31016
Cuturi, M. C.; Hill, M.; Amigorena, S.; Anegon, I.; Floto, R. A.; Chiffoleau, E.; et al.; Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation; Wiley Blackwell Publishing, Inc; American Journal of Transplantation; 14; 14-4-2014; 1021-1031
1600-6135
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31016
identifier_str_mv Cuturi, M. C.; Hill, M.; Amigorena, S.; Anegon, I.; Floto, R. A.; Chiffoleau, E.; et al.; Autologous dendritic cells prolong allograft survival through tmem176b-dependent antigen cross-presentation; Wiley Blackwell Publishing, Inc; American Journal of Transplantation; 14; 14-4-2014; 1021-1031
1600-6135
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com.gate2.inist.fr/doi/10.1111/ajt.12708/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/ajt.12708
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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 13.13397

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