Department of Pathology
Immunology and Infectious Disease | Medical Immunology
The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor 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 naive 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.
CTL, Eomes, Myc, TCR, immunology, metabolism, mouse, naive CD8 T cells
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Copyright © 2017, Wells et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Elife. 2017 Jul 24;6. doi: 10.7554/eLife.26398. Link to article on publisher's site
Wells, Alexandria C.; Daniels, Keith A.; Angelou, Constance C.; Fagerberg, Eric; Burnside, Amy S.; Markstein, Michele; Alfandari, Dominique; Welsh, Raymond M.; Pobezinskaya, Elena L.; and Pobezinsky, Leonid A., "Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells" (2017). Open Access Articles. 3200.
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This work is licensed under a Creative Commons Attribution 4.0 License.