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

Bibliographic Details
Main Author: Gordino, Gisela
Publication Date: 2021
Other Authors: Costa Pereira, Sara, Corredeira, Patrícia, Alves, Patrícia, Costa, Luis, Gomes, Anita Q., Silva-Santos, Bruno, Ribot, Julie
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/50776
Summary: © 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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spelling MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2CancerEffector T lymphocytesmiR-181amicroRNAsγδ T cells© 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.γδ 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 associates 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 critical regulator of human γδ T cell differentiation and highlight its potential for manipulation of γδ T cells in next-generation immunotherapies.This work was funded by the Fundação para a Ciência e Tecnologia (FCT) (IF/00013/2014 to J.C.R., SFRH/BD/128866/2017 to G.G.), Fundo de Investigação para a Saúde/INFARMED (FIS-FIS-2015-01_ONC_20150630-162 to J.C.R), and “la Caixa” Foundation (ID 100010434) under the agreement LCF/PR/HR19/52160011 (to B.S.-S.). We also acknowledge UIDB/50005/2020, project funded by Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES); and LISBOA-01-0145-FEDER-016394, project co-funded by FEDER from POR Lisboa 2020—Programa Operacional Regional de Lisboa, Portugal 2020, and Fundação para a Ciência e a Tecnologia.EMBO PressRepositório da Universidade de LisboaGordino, GiselaCosta Pereira, SaraCorredeira, PatríciaAlves, PatríciaCosta, LuisGomes, Anita Q.Silva-Santos, BrunoRibot, Julie2022-01-11T16:07:45Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50776engEMBO Rep. 2022 Jan 5;23(1):e522341469-221X10.15252/embr.2020522341469-3178info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:40:09Zoai:repositorio.ulisboa.pt:10451/50776Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:20:55.377848Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
title MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
spellingShingle MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
Gordino, Gisela
Cancer
Effector T lymphocytes
miR-181a
microRNAs
γδ T cells
title_short MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
title_full MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
title_fullStr MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
title_full_unstemmed MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
title_sort MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
author Gordino, Gisela
author_facet Gordino, Gisela
Costa Pereira, Sara
Corredeira, Patrícia
Alves, Patrícia
Costa, Luis
Gomes, Anita Q.
Silva-Santos, Bruno
Ribot, Julie
author_role author
author2 Costa Pereira, Sara
Corredeira, Patrícia
Alves, Patrícia
Costa, Luis
Gomes, Anita Q.
Silva-Santos, Bruno
Ribot, Julie
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Gordino, Gisela
Costa Pereira, Sara
Corredeira, Patrícia
Alves, Patrícia
Costa, Luis
Gomes, Anita Q.
Silva-Santos, Bruno
Ribot, Julie
dc.subject.por.fl_str_mv Cancer
Effector T lymphocytes
miR-181a
microRNAs
γδ T cells
topic Cancer
Effector T lymphocytes
miR-181a
microRNAs
γδ T cells
description © 2021 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
2022-01-11T16:07:45Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/50776
url http://hdl.handle.net/10451/50776
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv EMBO Rep. 2022 Jan 5;23(1):e52234
1469-221X
10.15252/embr.202052234
1469-3178
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv EMBO Press
publisher.none.fl_str_mv EMBO Press
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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