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MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2

2022-01Journal article Open access
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dc.contributor.authorGordino, Gisela
dc.contributor.authorCosta‐Pereira, Sara
dc.contributor.authorCorredeira, Patrícia
dc.contributor.authorAlves, Patrícia
dc.contributor.authorCosta, Luís
dc.contributor.authorGomes, Anita Q.
dc.contributor.authorSilva‐Santos, Bruno
dc.contributor.authorRibot, Julie C.
dc.date.accessioned2021-12-15T19:33:36Z
dc.date.available2021-12-15T19:33:36Z
dc.date.issued2022-01
dc.description.abstractγδ T cells are a conserved population of lymphocytes that contributes to anti-tumor responses through its overt type 1 inflammatory and cytotoxic properties. We have previously shown that human γδ T cells acquire this profile upon stimulation with IL-2 or IL-15, in a differentiation process dependent on MAPK/ERK signaling. Here, we identify microRNA-181a as a key modulator of human γδ T cell differentiation. We observe that miR-181a is highly expressed in patients with prostate cancer and that this pattern is associated with lower expression of NKG2D, a critical mediator of cancer surveillance. Interestingly, miR-181a expression negatively correlates with an activated type 1 effector profile obtained from in vitro differentiated γδ T cells and miR-181a overexpression restricts their levels of NKG2D and TNF-α. Upon in silico analysis, we identify two miR-181a candidate targets, Map3k2 and Notch2, which we validate via overexpression coupled with luciferase assays. These results reveal a novel role for miR-181a as a critical regulator of human γδ T cell differentiation and highlight its potential for manipulation of γδ T cells in next-generation immunotherapies.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGordino G, Costa-Pereira S, Corredeira P, Alves P, Costa L, Gomes AQ, et al. MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO Rep. 2022;23:e52234.pt_PT
dc.identifier.doi10.15252/embr.202052234pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/14061
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherEMBO Presspt_PT
dc.relation.publisherversionhttps://www.embopress.org/doi/full/10.15252/embr.202052234pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectCancerpt_PT
dc.subjectEffector T lymphocytespt_PT
dc.subjectmiR-181apt_PT
dc.subjectmicroRNAspt_PT
dc.subjectγδ T cellspt_PT
dc.titleMicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPagee52234pt_PT
oaire.citation.startPagee52234pt_PT
oaire.citation.titleEMBO reportspt_PT
oaire.citation.volume23pt_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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