Repository logo
 
No Thumbnail Available
Publication

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

Use this identifier to reference this record.

Advisor(s)

Abstract(s)

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.

Description

Keywords

Cancer Effector T lymphocytes miR-181a microRNAs γδ T cells

Citation

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.

Research Projects

Organizational Units

Journal Issue

Publisher

EMBO Press

Collections

Altmetrics