LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus

Nadia Cobo-Vuilleumier, Petra I. Lorenzo, Noelia García Rodríguez, Irene de Gracia Herrera Gómez, Esther Fuente-Martin, Livia López-Noriega, José Manuel Mellado-Gil, Silvana-Yanina Romero-Zerbo, Mathurin Baquié, Christian Claude Lachaud, Katja Stifter, German Perdomo, Marco Bugliani, Vincenzo De Tata, Domenico Bosco, Geraldine Parnaud, David Pozo, Abdelkrim Hmadcha, Javier P. Florido, Miguel G. Toscano, Peter de Haan, Kristina Schoonjans, Luis Sánchez Palazón, Piero Marchetti, Reinhold Schirmbeck, Alejandro Martín-Montalvo, Paolo Meda, Bernat Soria, Francisco-Javier Bermúdez-Silva, Luc St-Onge and Benoit R. Gauthier ()
Additional contact information
Nadia Cobo-Vuilleumier: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Petra I. Lorenzo: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Noelia García Rodríguez: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Irene de Gracia Herrera Gómez: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Esther Fuente-Martin: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Livia López-Noriega: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
José Manuel Mellado-Gil: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Silvana-Yanina Romero-Zerbo: Universidad de Málaga
Mathurin Baquié: Neurix SA
Christian Claude Lachaud: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Katja Stifter: Ulm University Hospital
German Perdomo: Universidad de Burgos
Marco Bugliani: University of Pisa—AOUP University Hospital
Vincenzo De Tata: University of Pisa
Domenico Bosco: University Hospital
Geraldine Parnaud: University Hospital
David Pozo: CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine
Abdelkrim Hmadcha: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Javier P. Florido: Consejería de Salud
Miguel G. Toscano: Amarna Therapeutics
Peter de Haan: Amarna Therapeutics
Kristina Schoonjans: EPFL
Luis Sánchez Palazón: CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine
Piero Marchetti: University of Pisa—AOUP University Hospital
Reinhold Schirmbeck: Ulm University Hospital
Alejandro Martín-Montalvo: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Paolo Meda: University of Geneva
Bernat Soria: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
Francisco-Javier Bermúdez-Silva: Universidad de Málaga
Benoit R. Gauthier: Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03943-0

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