MicroRNA-181a regulates IFN-γ expression in effector CD8+ T cell differentiation

  • 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.
Author:Tiago Amado, Ana Amorim, Francisco J. Enguita, Paula V. Romero, Daniel Inácio, Marta Pires de Miranda, Samantha J. WinterORCiDGND, J. Pedro Simas, Andreas KruegerORCiDGND, Nina Schmolka, Bruno Silva-Santos, Anita Q. Gomes
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/32002568
Parent Title (English):Journal of molecular medicine
Place of publication:Berlin ; Heidelberg ; New York, NY
Document Type:Article
Year of Completion:2020
Date of first Publication:2020/01/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/03/09
Tag:CD8+ T cell; IFN-γ expression; MicroRNA-181a
Page Number:12
First Page:309
Last Page:320
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/.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0