Repository logo
 
Publication

miR-181a negatively regulates human γδ T cell differentiation into anti-tumor effectors

2019-10Conference object Open access
Simple item page
dc.contributor.authorGordino, Gisela
dc.contributor.authorPereira, Sara
dc.contributor.authorGomes, Anita Q.
dc.contributor.authorsilva-Santos, Bruno
dc.contributor.authorRibot, Julie
dc.date.accessioned2020-03-23T18:42:10Z
dc.date.available2020-03-23T18:42:10Z
dc.date.issued2019-10
dc.description.abstractCytotoxicity and IFN-γ production by human γδ T cells underlie their potent anti-tumor functions. importantly, we have previously shown that ex vivo-isolated γδ thymocytes produced negligible IFN-γ and lacked cytolytic activity against leukemia cells but could acquire those properties upon stimulation with IL-2 or IL-15. This notwithstanding, the role of post-transcriptional mechanisms mediated by miRs in the acquisition of the γδ Th1-like phenotype remains unclear. By resorting to RNA-sequencing techniques, we have identified a discrete repertoire of miRs associated with this process, highlighting miR-181a as a potential regulator of γδ T cell functional differentiation. Strikingly, we have observed that miR-181a expression in γδ T cells could be altered by the presence of anti-inflammatory or pro-inflammatory cytokines, either upregulating or downregulation this miR levels, respectively, thus evidencing his role in modulating pathological responses elicited by γδ T cells. Importantly, in a series of gain-of-function experiments, we verified that miR-181a overexpression significantly impaired NKG2D, TNF-α and IFN-γ expression in the Vδ1+ subpopulation. additionally, the RT-PCR analysis of those samples allowed us to verify a decrease in the mRNA levels of genes linked to the cytotoxic potential of these cells. By using luciferase reporter technology, we have been able to validate Map3k2 and Notch2 as direct targets, through which miR-181a elicits his impairment of the Th1-like phenotype in γδ T cells. These findings may have major implications for the manipulation of γδ T cells in cancer immunotherapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGordino G, Costa-Pereira SA, Gomes AQ, Silva-Santos B, Ribot JC. miR-181a negatively regulates human γδ T cell differentiation into anti-tumor effectors. In: Tissue Environment in Health and Disease – Champalimaud Research Symposium, Lisboa, 8-10 de outubro de 2019. p. 45.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/11308
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttp://symposium.research.fchampalimaud.org/programme/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectImmune systempt_PT
dc.subjectmiR-181apt_PT
dc.subjectCancer immunotherapypt_PT
dc.subjectT cell differentiationpt_PT
dc.titlemiR-181a negatively regulates human γδ T cell differentiation into anti-tumor effectorspt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceLisboapt_PT
oaire.citation.endPage45pt_PT
oaire.citation.startPage45pt_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.typeconferenceObjectpt_PT
relation.isAuthorOfPublication2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875
relation.isAuthorOfPublication.latestForDiscovery2b5a3f0a-29c2-4ecd-a83f-50d0b99a4875

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
miR-181a negatively regulates human γδ T cell differentiation into anti-tumor effectors.pdf
Size:
6.03 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

ESTeSL - Posters