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The main cytokine associated with these protective responses is interferon-\u03b3 (IFN-\u03b3), whose production is known to be regulated at the transcriptional level during CD8<jats:sup>+<\/jats:sup> T cell differentiation. Here we found that microRNAs constitute a posttranscriptional brake to IFN-\u03b3 expression by CD8<jats:sup>+<\/jats:sup> T cells, since the genetic interference with the Dicer processing machinery resulted in the overproduction of IFN-\u03b3 by both thymic and peripheral CD8<jats:sup>+<\/jats:sup> T cells. Using a gene reporter mouse for IFN-\u03b3 locus activity, we compared the microRNA repertoires associated with the presence or absence of IFN-\u03b3 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 <jats:italic>mimics<\/jats:italic> in peripheral CD8<jats:sup>+<\/jats:sup> T cell cultures. We found that miR-181a limits IFN-\u03b3 production by suppressing the expression of the transcription factor <jats:italic>Id2<\/jats:italic>, which in turn promotes the <jats:italic>Ifng<\/jats:italic> expression program. Importantly, upon MuHV-4 challenge, miR-181a-deficient mice showed a more vigorous IFN-\u03b3<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> 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-\u03b3\u2013mediated effector CD8<jats:sup>+<\/jats:sup> T cell responses in vitro and in vivo.<\/jats:p>","DOI":"10.1007\/s00109-019-01865-y","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T07:03:07Z","timestamp":1580367787000},"page":"309-320","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["MicroRNA-181a regulates IFN-\u03b3 expression in effector CD8+ T cell differentiation"],"prefix":"10.1007","volume":"98","author":[{"given":"Tiago","family":"Amado","sequence":"first","affiliation":[]},{"given":"Ana","family":"Amorim","sequence":"additional","affiliation":[]},{"given":"Francisco J.","family":"Enguita","sequence":"additional","affiliation":[]},{"given":"Paula V.","family":"Romero","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"In\u00e1cio","sequence":"additional","affiliation":[]},{"given":"Marta Pires","family":"de Miranda","sequence":"additional","affiliation":[]},{"given":"Samantha J.","family":"Winter","sequence":"additional","affiliation":[]},{"given":"J. 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