Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells
- University of Massachusetts, United States
- University of Massachusetts Medical School, United States
Abstract
The differentiation of naïve CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful anti-viral, and anti-tumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naïve phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7 mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.
Article and author information
Author details
Dominique Alfandari
Leonid A Pobezinsky
Funding
National Multiple Sclerosis Society (PP-1503-03417)
- Leonid A Pobezinsky
University of Massachusetts Amherst (Start up funds)
- Leonid A Pobezinsky
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2014-0045, 2014-0065, 2015-0035) of the University of Massachusetts.
Copyright
© 2017, Wells et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells
eLife 6:e26398.
https://doi.org/10.7554/eLife.26398
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