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MicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiation

2020-01Journal article Open access
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dc.contributor.authorAmado, Tiago
dc.contributor.authorAmorim, Ana
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorRomero, Paula V.
dc.contributor.authorInácio, Daniel
dc.contributor.authorMiranda, Marta Pires
dc.contributor.authorWinter, Samantha J.
dc.contributor.authorSimas, J. Pedro
dc.contributor.authorKrueger, Andreas
dc.contributor.authorSchmolka, Nina
dc.contributor.authorSilva-Santos, Bruno
dc.contributor.authorGomes, Anita Q.
dc.date.accessioned2020-02-19T12:10:46Z
dc.date.available2020-02-19T12:10:46Z
dc.date.issued2020-01
dc.description.abstractCD8+ T cells are key players in immunity against intracellular infections and tumors. The main cytokine associated with these protective responses is interferon-γ (IFN-γ), whose production is known to be regulated at the transcriptional level during CD8+ T cell differentiation. Here we found that microRNAs constitute a posttranscriptional brake to IFN-γ expression by CD8+ T cells since the genetic interference with the Dicer processing machinery resulted in the overproduction of IFN-γ by both thymic and peripheral CD8+ T cells. Using a gene reporter mouse for IFN-γ locus activity, we compared the microRNA repertoires associated with the presence or absence of IFN-γ expression. This allowed us to identify a set of candidates, including miR-181a and miR-451, which were functionally tested in overexpression experiments using synthetic mimics in peripheral CD8+ T cell cultures. We found that miR-181a limits IFN-γ production by suppressing the expression of the transcription factor Id2, which in turn promotes the Ifng expression program. Importantly, upon the MuHV-4 challenge, miR-181a-deficient mice showed a more vigorous IFN-γ+ CD8+ T cell response and were able to control viral infection significantly more efficiently than control mice. These data collectively establish a novel role for miR-181a in regulating IFN-γ-mediated effector CD8+ T cell responses in vitro and in vivo.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAmado T, Amorim A, Enguita FJ, Romero PV, Inácio D, Gomes AQ, et al. MicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiation. J Mol Med. 2020;98(2):309-20.pt_PT
dc.identifier.doi10.1007/s00109-019-01865-ypt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/11115
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_PT
dc.relation.publisherversionhttps://link.springer.com/article/10.1007%2Fs00109-019-01865-ypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectMicroRNA-181apt_PT
dc.subjectIFN-γ expressionpt_PT
dc.subjectCD8+ T cellpt_PT
dc.titleMicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage320pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage309pt_PT
oaire.citation.titleJournal of Molecular Medicinept_PT
oaire.citation.volume98pt_PT
person.familyNameGomes
person.givenNameAnita
person.identifier.ciencia-id4B10-E015-52B7
person.identifier.orcid0000-0002-3348-0448
person.identifier.ridC-3580-2014
person.identifier.scopus-author-id7202386033
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875
relation.isAuthorOfPublication.latestForDiscovery2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875

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