LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype

The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hy...

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Autores: Cobo-Vuilleumier, Nadia, Rodríguez-Fernandez, Silvia, López-Noriega, Livia, Lorenzo, Petra I., Franco, Jaime M., Lachaud, Christian C., Martín-Vázquez, Eugenia, Legido, Raquel Araujo, Dorronsoro, Akaitz, López-Férnandez-Sobrino, Raul, Fernández-Santos, Beatriz, Espejo Serrano, Carmen, Salas-Lloret, Daniel, van Overbeek, Nila, Ramos-Rodriguez, Mireia, Mateo-Rodríguez, Carmen, Hidalgo, Lucia, Marin-Canas, Sandra, Nano, Rita, Arroba, Ana I., Campos Caro, Antonio, Vertegaal, Alfred C. O., Martín-Montalvo, Alejandro, Martín, Franz, Aguilar-Diosdado, Manuel, Piemonti, Lorenzo, Pasquali, Lorenzo, González Prieto, Roman, García Sánchez, Maria Isabel, Eizirik, Decio L., Martínez-Brocca, Maria Asuncion, Vives-Pi, Marta, Gauthier, Benoit R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/387211
Acceso en línea:http://hdl.handle.net/10261/387211
Access Level:acceso abierto
Palabra clave:Autoimmune diseases
Drug development
Immune tolerance
Pancreatic islets
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dc.title.none.fl_str_mv LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
title LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
spellingShingle LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
Cobo-Vuilleumier, Nadia
Autoimmune diseases
Drug development
Immune tolerance
Pancreatic islets
title_short LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
title_full LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
title_fullStr LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
title_full_unstemmed LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
title_sort LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype
dc.creator.none.fl_str_mv Cobo-Vuilleumier, Nadia
Rodríguez-Fernandez, Silvia
López-Noriega, Livia
Lorenzo, Petra I.
Franco, Jaime M.
Lachaud, Christian C.
Martín-Vázquez, Eugenia
Legido, Raquel Araujo
Dorronsoro, Akaitz
López-Férnandez-Sobrino, Raul
Fernández-Santos, Beatriz
Espejo Serrano, Carmen
Salas-Lloret, Daniel
van Overbeek, Nila
Ramos-Rodriguez, Mireia
Mateo-Rodríguez, Carmen
Hidalgo, Lucia
Marin-Canas, Sandra
Nano, Rita
Arroba, Ana I.
Campos Caro, Antonio
Vertegaal, Alfred C. O.
Martín-Montalvo, Alejandro
Martín, Franz
Aguilar-Diosdado, Manuel
Piemonti, Lorenzo
Pasquali, Lorenzo
González Prieto, Roman
García Sánchez, Maria Isabel
Eizirik, Decio L.
Martínez-Brocca, Maria Asuncion
Vives-Pi, Marta
Gauthier, Benoit R.
author Cobo-Vuilleumier, Nadia
author_facet Cobo-Vuilleumier, Nadia
Rodríguez-Fernandez, Silvia
López-Noriega, Livia
Lorenzo, Petra I.
Franco, Jaime M.
Lachaud, Christian C.
Martín-Vázquez, Eugenia
Legido, Raquel Araujo
Dorronsoro, Akaitz
López-Férnandez-Sobrino, Raul
Fernández-Santos, Beatriz
Espejo Serrano, Carmen
Salas-Lloret, Daniel
van Overbeek, Nila
Ramos-Rodriguez, Mireia
Mateo-Rodríguez, Carmen
Hidalgo, Lucia
Marin-Canas, Sandra
Nano, Rita
Arroba, Ana I.
Campos Caro, Antonio
Vertegaal, Alfred C. O.
Martín-Montalvo, Alejandro
Martín, Franz
Aguilar-Diosdado, Manuel
Piemonti, Lorenzo
Pasquali, Lorenzo
González Prieto, Roman
García Sánchez, Maria Isabel
Eizirik, Decio L.
Martínez-Brocca, Maria Asuncion
Vives-Pi, Marta
Gauthier, Benoit R.
author_role author
author2 Rodríguez-Fernandez, Silvia
López-Noriega, Livia
Lorenzo, Petra I.
Franco, Jaime M.
Lachaud, Christian C.
Martín-Vázquez, Eugenia
Legido, Raquel Araujo
Dorronsoro, Akaitz
López-Férnandez-Sobrino, Raul
Fernández-Santos, Beatriz
Espejo Serrano, Carmen
Salas-Lloret, Daniel
van Overbeek, Nila
Ramos-Rodriguez, Mireia
Mateo-Rodríguez, Carmen
Hidalgo, Lucia
Marin-Canas, Sandra
Nano, Rita
Arroba, Ana I.
Campos Caro, Antonio
Vertegaal, Alfred C. O.
Martín-Montalvo, Alejandro
Martín, Franz
Aguilar-Diosdado, Manuel
Piemonti, Lorenzo
Pasquali, Lorenzo
González Prieto, Roman
García Sánchez, Maria Isabel
Eizirik, Decio L.
Martínez-Brocca, Maria Asuncion
Vives-Pi, Marta
Gauthier, Benoit R.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Junta de Andalucía
Instituto de Salud Carlos III
Fundación de la Sociedad Española de Diabetes
Generalitat de Catalunya
European Commission
Fundación Progreso y Salud
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación (España)
Fundación DiabetesCERO
National Institutes of Health (US)
Fonds de La Recherche Scientifique (Belgique)
Lachaud, Christian C. [0000-0001-8698-4589]
Martín, Franz [0000-0002-5745-8704]
Gauthier, Benoit R. [0000-0001-8146-7486]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Autoimmune diseases
Drug development
Immune tolerance
Pancreatic islets
topic Autoimmune diseases
Drug development
Immune tolerance
Pancreatic islets
description The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/387211
url http://hdl.handle.net/10261/387211
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-83588-P
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-123083NB-I00
https://doi.org/10.1002/ctm2.70134

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotypeCobo-Vuilleumier, NadiaRodríguez-Fernandez, SilviaLópez-Noriega, LiviaLorenzo, Petra I.Franco, Jaime M.Lachaud, Christian C.Martín-Vázquez, EugeniaLegido, Raquel AraujoDorronsoro, AkaitzLópez-Férnandez-Sobrino, RaulFernández-Santos, BeatrizEspejo Serrano, CarmenSalas-Lloret, Danielvan Overbeek, NilaRamos-Rodriguez, MireiaMateo-Rodríguez, CarmenHidalgo, LuciaMarin-Canas, SandraNano, RitaArroba, Ana I.Campos Caro, AntonioVertegaal, Alfred C. O.Martín-Montalvo, AlejandroMartín, FranzAguilar-Diosdado, ManuelPiemonti, LorenzoPasquali, LorenzoGonzález Prieto, RomanGarcía Sánchez, Maria IsabelEizirik, Decio L.Martínez-Brocca, Maria AsuncionVives-Pi, MartaGauthier, Benoit R.Autoimmune diseasesDrug developmentImmune tolerancePancreatic isletsThe complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival.We thank Dr Maria José Quintero from the Cytometry Core Facility and the team from the Genomic Core Facility of CABIMER, as well as Pedro Antonio Soriano Fernandez and Noelia García Rodríguez for their excellent technical support. Special thanks to all donors and to the Biobank Node of the Hospital Virgen Macarena (Biobanco del Sistema Sanitario Público de Andalucía) which is part of the Spanish National biobanks Network (PT20/00069) supported by Instituto Carlos III and FEDER funds. We acknowledge the support of the Basic Experimentation in Diabetes study group of the Spanish Association of Diabetes as well as positive discussion through the Consolidated Research Group 2021 SGR 00002, AGAUR, Generalitat de Catalunya. We also acknowledge the use of DeepL write and ChatGTP for English editing purposes. The authors are supported by grants from the Consejería de Salud y Consumo, Fundación Pública Andaluza Progreso y Salud, Junta de Andalucía (PI-0727-2010 and PI-0001-2020 to B. R. G), the Consejería de Economía, Innovación y Ciencia (P10.CTS.6359 to B. R. G and DOC_00652, FSE and Lema: Andalucía moves with Europe to L. L. N.), the Ministerio de Ciencia E Innovación (BFU2017-83588-P, PID2021-123083NB-I00 financed by MCIN/AEI/10.13039/501100011033 and by FEDER, UE to B. R. G.), the DiabetesCERO Foundation (B. R. G.), the Spanish Diabetes Society (B. R. G.) and the Juvenile Diabetes Research Foundation/Breakthrough TD1 (17-2013-372, 2-SRA-2019-837-S-B, 3-SRA-2023-1307-S-B to B. R. G; 3-SRA-2022-1201-S-B(1) to D. L. E.), the National Institutes of Health Human Islet Research Network Consortium on Beta Cell Death & Survival from Pancreatic Beta Cell Gene Networks to Therapy [HIRN-CBDS], (U01 DK127786 to D. L. E.) and the National Institutes of Health, NIDDK (RO1DK126444 and RO1DK133881-01 to D. L. E.). P. A. S. F. is contracted through an action funded by the EU- NextGenerationEU, and the Recovery, Transformation and Resilience Plan (SE/INV/0008/2022) granted to the Consejería de Empleo, Formación y Trabajo Autónomo of the Junta de Andalucía in the 2022 call of the Investigo Program, Mechanism for Recovery and Resilience. E. M. V. is the recipient of a post-doctoral fellowship from the Belgian FNRS.Peer reviewedJohn Wiley & SonsJunta de AndalucíaInstituto de Salud Carlos IIIFundación de la Sociedad Española de DiabetesGeneralitat de CatalunyaEuropean CommissionFundación Progreso y SaludAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Ministerio de Ciencia e Innovación (España)Fundación DiabetesCERONational Institutes of Health (US)Fonds de La Recherche Scientifique (Belgique)Lachaud, Christian C. [0000-0001-8698-4589]Martín, Franz [0000-0002-5745-8704]Gauthier, Benoit R. [0000-0001-8146-7486]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/387211reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-83588-Pinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-123083NB-I00https://doi.org/10.1002/ctm2.70134Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3872112026-05-22T06:33:51Z
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