Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells
Authors
Wells, Alexandria C.Daniels, Keith A.
Angelou, Constance C.
Fagerberg, Eric
Burnside, Amy S.
Markstein, Michele
Alfandari, Dominique
Welsh, Raymond M.
Pobezinskaya, Elena L.
Pobezinsky, Leonid A.
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2017-07-24Keywords
CTLEomes
Myc
TCR
immunology
metabolism
mouse
naive CD8 T cells
Immunology and Infectious Disease
Medical Immunology
Metadata
Show full item recordAbstract
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.Source
Elife. 2017 Jul 24;6. doi: 10.7554/eLife.26398. Link to article on publisher's siteDOI
10.7554/eLife.26398Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40395PubMed ID
28737488Related Resources
Rights
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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.26398
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Except where otherwise noted, this item's license is described as 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.