The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs
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2016Metadata
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Doñas, Cristian
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The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs
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© 2016 The Authors As it has been established that demethylation of lysine 27 of histone H3 by the lysine-specific demethylase 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-β1, and reduced secretion of proinflammatory cytokines IL-6, IFN-γ, 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 CD4+ T cells infiltrating the central nervous s
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URI: https://repositorio.uchile.cl/handle/2250/153994
DOI: 10.1016/j.jaut.2016.07.011
ISSN: 10959157
08968411
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Journal of Autoimmunity, Volumen 75,
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