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Authordc.contributor.authorDoñas, Cristian
Authordc.contributor.authorNeira, Jocelyn
Authordc.contributor.authorOsorio Barrios, Francisco
Authordc.contributor.authorCarrasco, Macarena
Authordc.contributor.authorFernández, Dominique
Authordc.contributor.authorPrado, Carolina
Authordc.contributor.authorLoyola, Alejandra
Authordc.contributor.authorPacheco, Rodrigo
Authordc.contributor.authorRosemblatt Silber, Mario César
Cita de ítemdc.identifier.citationScientifc Reports (2021) 11:1342es_ES
Abstractdc.description.abstractDendritic cells (DCs) promote T-cell mediated tolerance to self-antigens and induce inflammation to innocuous-antigens. This dual potential makes DCs fundamental players in inflammatory disorders. Evidence from inflammatory colitis mouse models and inflammatory bowel diseases (IBD) patients indicated that gut inflammation in IBD is driven mainly by T-helper-1 (Th1) and Th17 cells, suggesting an essential role for DCs in the development of IBD. Here we show that GSK-J4, a selective inhibitor of the histone demethylase JMJD3/UTX, attenuated inflammatory colitis by reducing the inflammatory potential and increasing the tolerogenic features of DCs. Mechanistic analyses revealed that GSK-J4 increased activating epigenetic signals while reducing repressive marks in the promoter of retinaldehyde dehydrogenase isoforms 1 and 3 in DCs, enhancing the production of retinoic acid. This, in turn, has an impact on regulatory T cells (Treg) increasing their lineage stability and gut tropism as well as potentiating their suppressive activity. Our results open new avenues for the treatment of IBD patients.es_ES
Patrocinadordc.description.sponsorshipPrograma de Apoyo a Centros con Financiamiento Basal from "Comision Nacional de Investigacion Cientifica y Tecnologica de Chile (CONICYT)" AFB-170004 Fondo Nacional de Desarrollo Cientifico y Tecnologico de Chile FONDECYT-1200577 FONDECYT-1170093 FONDECYT-11190251es_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
Link to Licensedc.rights.uri*
Sourcedc.sourceScientifc Reportses_ES
Títulodc.titleThe demethylase inhibitor GSK‑J4 limits infammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cellses_ES
Document typedc.typeArtículo de revistaes_ES
dc.description.versiondc.description.versionVersión publicada - versión final del editores_ES
dcterms.accessRightsdcterms.accessRightsAcceso abiertoes_ES
Indexationuchile.indexArtículo de publícación WoSes_ES

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Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States