Doñas, CristianCarrasco, MacarenaFritz, MacarenaPrado, CarolinaTejón, GabrielaOsorio-Barrios, FranciscoManríquez, ValeriaReyes, PazPacheco, RodrigoBono, María RosaLoyola, AlejandraRosemblatt, Mario2023-08-232023-08-232016-12Journal of Autoimmunity. Volume 75, Pages 105 - 117. 1 December 20160896-8411https://repositorio.unab.cl/xmlui/handle/ria/52768Indexación: Scopus.As it has been established that demethylation of lysine 27 of histone H3 by the lysine-specific deme thylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize that inhibition of JMJD3 may attenuate autoimmune disorders. We found that in vivo administration of GSK-J4, a selective inhibitor of JMJD3 and UTX, ameliorates the severity of experimental autoimmune encephalomyelitis (EAE). In vitro experiments revealed that the anti-inflammatory effect of GSK-J4 was exerted through an effect on dendritic cells (DCs), promoting a tolerogenic profile characterized by reduced expression of costimulatory molecules CD80/CD86, an increased expression of tolerogenic molecules CD103 and TGF-b1, and reduced secretion of proin flammatory cytokines IL-6, IFN-g, and TNF. Adoptive transfer of GSK-J4-treated DCs into EAE mice reduced the clinical manifestation of the disease and decreased the extent of inflammatory CD4þ T cells infiltrating the central nervous system. Notably, Treg generation, stability, and suppressive activity were all exacerbated by GSK-J4-treated DCs without affecting Th1 and Th17 cell production. Our data show that GSK-J4-mediated modulation of inflammation is achieved by a direct effect on DCs and that systemic treatment with GSK-J4 or adoptive transfer of GSK-J4-treated DCs ex vivo may be promising approaches for the treatment of inflammatory and autoimmune disorders. © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).enGSK-J4AutoimmunityDCsTregJMJD3H3K27me3ArtículoAtribution 4.0 International (CC BY 4.0)10.1016/j.jaut.2016.07.011