Cobo-Vuilleumier, NadiaLorenzo, Petra I.García Rodríguez, NoeliaHerrera Gómez, Irene de GraciaFuente-Martin, EstherLópez-Noriega, LiviaMellado-Gil, José ManuelRomero-Zerbo, Silvana-YaninaBaquié, MathurinLachaud, Christian ClaudeStifter, KatjaGerman, PerdomoMarco, BuglianiDe Tata, VincenzoBosco, DomenicoParnaud, GeraldinePozo, DavidHmadcha, AbdelkrimFlorido, Javier P.Toscano, Miguel G.de Haan, PeterSchoonjans, KristinaSánchez Palazón, LuisMarchetti, PieroSchirmbeck, ReinholdMartín-Montalvo, AlejandroMeda, PaoloSoria, BernatBermúdez-Silva, Francisco-JavierSt-Onge, LucGauthier, Benoit R.2018-04-192018-04-192018-04-16Cobo-Vuilleumier, N; Lorenzo, PI; García Rodríguez, N; Herrera Gómez, IG; Fuente-Martin, E; López-Noriega, L, et al. LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus. Nature Communications. 2018;9(1):1488http://hdl.handle.net/10668/2858Type 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.enIslets of LangerhansType 1 diabetesType 2 diabetesIslotes PancreáticosDiabetes Mellitus Tipo 1Diabetes Mellitus Tipo 2Diabetes MellitusDiabetesMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 1Medical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Anatomy::Endocrine System::Endocrine Glands::Islets of LangerhansMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes MellitusMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::MurinaeMedical Subject Headings::Organisms::Eukaryota::Animalsresearch articleopen access10.1038/s41467-018-03943-02041-1723