The demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cells

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dc.contributor.authorDoñas, C.
dc.contributor.authorNeira, J.
dc.contributor.authorOsorio-Barrios, F.
dc.contributor.authorCarrasco, M.
dc.contributor.authorFernández, D.
dc.contributor.authorPrado, C.
dc.contributor.authorLoyola, A.
dc.contributor.authorPacheco, R.
dc.contributor.authorRosemblatt, M.
dc.date.accessioned2021-05-10T21:55:48Z
dc.date.available2021-05-10T21:55:48Z
dc.date.issued2021-12
dc.descriptionIndexación Scopuses
dc.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. © 2021, The Author(s).es
dc.description.urihttps://www-nature-com.recursosbiblioteca.unab.cl/articles/s41598-020-79122-3
dc.identifier.citationScientific Reports Volume 11, Issue 1, December 2021, Article number 1342es
dc.identifier.doi10.1038 / s41598-020-79122-3
dc.identifier.issn20452322
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/18822
dc.language.isoenes
dc.publisherNature Researches
dc.subjectRetinoic Acides
dc.subjectDendritic Cellses
dc.subjectRetinoles
dc.titleThe demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cellses
dc.typeArtículoes
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