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 |
| id |
ES_c8d314decdecade9de8bb563e4dd183a |
|---|---|
| oai_identifier_str |
oai:digital.csic.es:10261/387211 |
| network_acronym_str |
ES |
| network_name_str |
España |
| spelling |
LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype 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. Autoimmune diseases Drug development Immune tolerance Pancreatic islets 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. 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 reviewed John Wiley & Sons http://hdl.handle.net/10261/387211 |
| 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 |
| 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 |
| topic |
Autoimmune diseases Drug development Immune tolerance Pancreatic islets |
| topic_facet |
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 |
| format |
article |
| status_str |
publishedVersion |
| url |
http://hdl.handle.net/10261/387211 |
| eu_rights_str_mv |
openAccess |
| publisher |
John Wiley & Sons |
| institution |
Consejo Superior de Investigaciones Científicas (CSIC) |
| collection |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| reponame_str |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| instname_str |
Consejo Superior de Investigaciones Científicas (CSIC) |
| _version_ |
1878440656851959808 |
| publishDateSort |
2024 |
| author_browse |
Aguilar-Diosdado, Manuel Arroba, Ana I. Campos Caro, Antonio Cobo-Vuilleumier, Nadia Dorronsoro, Akaitz Eizirik, Decio L. Espejo Serrano, Carmen Fernández-Santos, Beatriz Franco, Jaime M. García Sánchez, Maria Isabel Gauthier, Benoit R. González Prieto, Roman Hidalgo, Lucia Lachaud, Christian C. Legido, Raquel Araujo Lorenzo, Petra I. López-Férnandez-Sobrino, Raul López-Noriega, Livia Marin-Canas, Sandra Martín, Franz Martín-Montalvo, Alejandro Martín-Vázquez, Eugenia Martínez-Brocca, Maria Asuncion Mateo-Rodríguez, Carmen Nano, Rita Pasquali, Lorenzo Piemonti, Lorenzo Ramos-Rodriguez, Mireia Rodríguez-Fernandez, Silvia Salas-Lloret, Daniel Vertegaal, Alfred C. O. Vives-Pi, Marta van Overbeek, Nila |
| publisherStr |
John Wiley & Sons |
| score |
6,9303427 |