MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/50776 |
Resumo: | © 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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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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-20T18:11:04Zoai:repositorio.ul.pt:10451/50776Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T18:11:04Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| 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 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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EMBO Press |
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EMBO Press |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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mluisa.alvim@gmail.com |
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