Publicação
MicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiation
| dc.contributor.author | Amado, Tiago | |
| dc.contributor.author | Amorim, Ana | |
| dc.contributor.author | Enguita, Francisco J. | |
| dc.contributor.author | Romero, Paula V. | |
| dc.contributor.author | Inácio, Daniel | |
| dc.contributor.author | Miranda, Marta Pires | |
| dc.contributor.author | Winter, Samantha J. | |
| dc.contributor.author | Simas, J. Pedro | |
| dc.contributor.author | Krueger, Andreas | |
| dc.contributor.author | Schmolka, Nina | |
| dc.contributor.author | Silva-Santos, Bruno | |
| dc.contributor.author | Gomes, Anita Q. | |
| dc.date.accessioned | 2020-02-19T12:10:46Z | |
| dc.date.available | 2020-02-19T12:10:46Z | |
| dc.date.issued | 2020-01 | |
| dc.description.abstract | CD8+ 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.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Amado 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.doi | 10.1007/s00109-019-01865-y | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.21/11115 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Springer | pt_PT |
| dc.relation.publisherversion | https://link.springer.com/article/10.1007%2Fs00109-019-01865-y | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | pt_PT |
| dc.subject | MicroRNA-181a | pt_PT |
| dc.subject | IFN-γ expression | pt_PT |
| dc.subject | CD8+ T cell | pt_PT |
| dc.title | MicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiation | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 320 | pt_PT |
| oaire.citation.issue | 2 | pt_PT |
| oaire.citation.startPage | 309 | pt_PT |
| oaire.citation.title | Journal of Molecular Medicine | pt_PT |
| oaire.citation.volume | 98 | pt_PT |
| person.familyName | Gomes | |
| person.givenName | Anita | |
| person.identifier.ciencia-id | 4B10-E015-52B7 | |
| person.identifier.orcid | 0000-0002-3348-0448 | |
| person.identifier.rid | C-3580-2014 | |
| person.identifier.scopus-author-id | 7202386033 | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | 2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875 | |
| relation.isAuthorOfPublication.latestForDiscovery | 2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875 |
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