ArticleNature communications2018
LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.
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Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
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39 citing papers in PubMed, 64 citations in OpenAlex.
- From hepatic to hematopoietic: LRH-1's expanding cellular repertoire to the immune system.The FEBS journal · 2026Review
- Microbiome-host communication via vaccenic acid modulates LRH-1/NR5A2 activity and ameliorates metabolic liver disease.EMBO molecular medicine · 2026Article
- Structure-guided compound prioritization strategy for virtual screening identifies putative binders for the nuclear receptor LRH-1.bioRxiv : the preprint server for biology · 2026Article
- Exploring the Expanding Role of Nuclear Receptor LRH-1/NR5A2 in Cell Biology and Immunity.International journal of cell biology · 2026Review
- Co-treatments of vitamin D and mesenchymal stem cells effectively alleviate the diabetic kidney disease through attenuating the SIRT1-mediated pathways.Stem cell research & therapy · 2025Article
- Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025Review
- Review
- LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.Clinical and translational medicine · 2024Article
- Islet cell spheroids produced by a thermally sensitive scaffold: a new diabetes treatment.Journal of nanobiotechnology · 2024Article
- Hepatocyte-specific NR5A2 deficiency induces pyroptosis and exacerbates non-alcoholic steatohepatitis by downregulating ALDH1B1 expression.Cell death & disease · 2024Article
- Liver receptor homolog-1: structures, related diseases, and drug discovery.Acta pharmacologica Sinica · 2024Review
- Enhancing human islet xenotransplant survival and function in diabetic immunocompetent mice through LRH-1/NR5A2 pharmacological activation.Frontiers in immunology · 2024Article
- LRH-1 activation alleviates diabetes-induced podocyte injury by promoting GLS2-mediated glutaminolysis.Cell proliferation · 2023Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- New High-Throughput Screen Discovers Novel Ligands of Full-Length Nuclear Receptor LRH-1.ACS chemical biology · 2023Article
- Nuclear receptor 5A2 regulation of Agrp underlies olanzapine-induced hyperphagia.Molecular psychiatry · 2023Review
- Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses.Frontiers in cell and developmental biology · 2023Article
- The PTGS2/COX2-PGEInternational journal of biological sciences · 2023Review
- PPARs at the crossroads of T cell differentiation and type 1 diabetes.Frontiers in immunology · 2023Review
- A phospholipid mimetic targeting LRH-1 ameliorates colitis.Cell chemical biology · 2022Article
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Authors and funding
31 authors at 10 institutions in 4 countries.
Nadia Cobo-VuilleumierDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Petra I LorenzoDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Noelia García RodríguezDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Irene de Gracia Herrera GómezDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Esther Fuente-MartinDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Livia López-NoriegaDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
José Manuel Mellado-GilDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Silvana-Yanina Romero-ZerboUnidad de Gestión Clínica Intercentros de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA) Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, 29010, Spain.
Mathurin BaquiéNeurix SA, Geneva, 1228, Switzerland.
Christian Claude LachaudDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Katja StifterUlm University Hospital, Ulm, 89081, Germany.
German PerdomoFacultad de Ciencias de la Salud, Universidad de Burgos, Burgos, 09001, Spain.
Marco BuglianiDepartment Clinical and Experimental Medicine, University of Pisa-AOUP University Hospital, Pisa, 56126, Italy.
Vincenzo De TataDepartment of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, 56126, Italy.
Domenico BoscoCell Isolation and Transplantation Centre, University Hospital, Geneva, 1211, Switzerland.
Geraldine ParnaudCell Isolation and Transplantation Centre, University Hospital, Geneva, 1211, Switzerland.
David PozoDepartment of Cell Dynamics and Signalling, CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville, 41092, Spain.ORCID http://orcid.org/0000-0002-3732-4960
Abdelkrim HmadchaDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.ORCID http://orcid.org/0000-0002-4105-3702
Javier P FloridoClinical Bioinformatics Area, Fundación Progreso y Salud, Consejería de Salud, Seville, 41013, Spain.
Miguel G ToscanoAmarna Therapeutics, Seville, 41092, Spain.
Peter de HaanAmarna Therapeutics, Seville, 41092, Spain.
Kristina SchoonjansLaboratory of Metabolic Signaling, EPFL, Lausanne, 1015, Switzerland.
Luis Sánchez PalazónBiological Resources, CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville, 41092, Spain.
Piero MarchettiDepartment Clinical and Experimental Medicine, University of Pisa-AOUP University Hospital, Pisa, 56126, Italy.
Reinhold SchirmbeckUlm University Hospital, Ulm, 89081, Germany.
Alejandro Martín-MontalvoDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Paolo MedaDepartment of Cell Physiology and Metabolism, University of Geneva, Geneva, 1211, Switzerland.
Bernat SoriaDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain.
Francisco-Javier Bermúdez-SilvaUnidad de Gestión Clínica Intercentros de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA) Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, 29010, Spain.ORCID http://orcid.org/0000-0003-3133-9691
Luc St-Onge, Neuried, Munich, 82061, Germany.
Benoit R GauthierDepartment of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, 41092, Spain. benoit.gauthier@cabimer.es.ORCID http://orcid.org/0000-0001-8146-7486
Centro Andaluz de Biología Molecular y Medicina Regenerativa · ESCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas · ESUniversity of Pisa · ITUniversity Hospital of Geneva · CHUniversity Hospital Ulm · DEÉcole Polytechnique Fédérale de Lausanne · CHFundación Progreso y Salud · ESMax Planck Institute of Neurobiology · DEUniversidad de Burgos · ESUniversity of Geneva · CH
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.
Indexed as
AnimalsApoptosisCell CommunicationCell SurvivalDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2FemaleGene Expression RegulationHumansHypoglycemic AgentsImmunity, InnateInsulinInsulin-Secreting CellsIslets of LangerhansIslets of Langerhans TransplantationMacrophagesHypoglycemic AgentsInsulinNr5a2 protein, mousePhenalenesReceptors, Cytoplasmic and NuclearStreptozocin
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