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Gordino G, Costa-Pereira S, Corredeira P, et al. MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO Rep. 2021;23(1):e52234doi: 10.15252/embr.202052234.
Gordino, G., Costa-Pereira, S., Corredeira, P., Alves, P., Costa, L., Gomes, A. Q., Silva-Santos, B., & Ribot, J. C. (2022). MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO reports, 23(1), e52234. https://doi.org/10.15252/embr.202052234
Gordino, Gisela, et al. "MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2." EMBO reports vol. 23,1 (2022): e52234. doi: https://doi.org/10.15252/embr.202052234
Gordino G, Costa-Pereira S, Corredeira P, Alves P, Costa L, Gomes AQ, Silva-Santos B, Ribot JC. MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO Rep. 2022 Jan 05;23(1):e52234. doi: 10.15252/embr.202052234. Epub 2021 Nov 24. PMID: 34821000; PMCID: PMC8728617.
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EMBO Rep. 2022 Jan 05;23(1):e52234. doi: 10.15252/embr.202052234. Epub 2021 Nov 24.

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

EMBO reports

Gisela Gordino, Sara Costa-Pereira, Patrícia Corredeira, Patrícia Alves, Luís Costa, Anita Q Gomes, Bruno Silva-Santos, Julie C Ribot

Affiliations

  1. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
  2. Medical Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
  3. Escola Superior de Tecnologia da Saúde de Lisboa, Lisbon, Portugal.

PMID: 34821000 PMCID: PMC8728617 DOI: 10.15252/embr.202052234

Abstract

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.

© 2021 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords: cancer; effector T lymphocytes; miR-181a; microRNAs; γδ T cells

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