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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| 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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oai:digital.csic.es:10261/387211 |
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España |
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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 |
| dc.relation.none.fl_str_mv |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
John Wiley & Sons |
| publisher.none.fl_str_mv |
John Wiley & Sons |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869419318944464896 |
| 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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15.81155 |