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http://hdl.handle.net/10400.21/14061
Título: | MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2 |
Autor: | Gordino, Gisela Costa‐Pereira, Sara Corredeira, Patrícia Alves, Patrícia Costa, Luís Gomes, Anita Q. Silva‐Santos, Bruno Ribot, Julie C. |
Palavras-chave: | Cancer Effector T lymphocytes miR-181a microRNAs γδ T cells |
Data: | Jan-2022 |
Editora: | EMBO Press |
Citação: | Gordino 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. |
Resumo: | 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 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. |
Peer review: | yes |
URI: | http://hdl.handle.net/10400.21/14061 |
DOI: | 10.15252/embr.202052234 |
Versão do Editor: | https://www.embopress.org/doi/full/10.15252/embr.202052234 |
Aparece nas colecções: | ESTeSL - Artigos |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2.pdf | 1,52 MB | Adobe PDF | Ver/Abrir |
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