TY  - JOUR
A1  - Amado, Tiago
A1  - Amorim, Ana
A1  - Enguita, Francisco J.
A1  - Romero, Paula V.
A1  - Inácio, Daniel
A1  - Miranda, Marta Pires de
A1  - Winter, Samantha J.
A1  - Simas, J. Pedro
A1  - Krueger, Andreas
A1  - Schmolka, Nina
A1  - Silva-Santos, Bruno
A1  - Gomes, Anita Q.
T1  - MicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiation
T2  - Journal of molecular medicine
N2  - CD8+ T cells are key players in immunity against intracellular infections and tumors. The main cytokine associated with these protective responses is interferon-γ (IFN-γ), whose production is known to be regulated at the transcriptional level during CD8+ T cell differentiation. Here we found that microRNAs constitute a posttranscriptional brake to IFN-γ expression by CD8+ T cells, since the genetic interference with the Dicer processing machinery resulted in the overproduction of IFN-γ by both thymic and peripheral CD8+ T cells. Using a gene reporter mouse for IFN-γ locus activity, we compared the microRNA repertoires associated with the presence or absence of IFN-γ expression. This allowed us to identify a set of candidates, including miR-181a and miR-451, which were functionally tested in overexpression experiments using synthetic mimics in peripheral CD8+ T cell cultures. We found that miR-181a limits IFN-γ production by suppressing the expression of the transcription factor Id2, which in turn promotes the Ifng expression program. Importantly, upon MuHV-4 challenge, miR-181a-deficient mice showed a more vigorous IFN-γ+ CD8+ T cell response and were able to control viral infection significantly more efficiently than control mice. These data collectively establish a novel role for miR-181a in regulating IFN-γ–mediated effector CD8+ T cell responses in vitro and in vivo.
KW  - MicroRNA-181a
KW  - IFN-γ expression
KW  - CD8+ T cell
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53075
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-530758
SN  - 0946-2716
SN  - 1432-1440
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 98
IS  - 2
SP  - 309
EP  - 320
PB  - Springer
CY  - Berlin ; Heidelberg ; New York, NY
ER  -