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Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells.

ABSTRACT: 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.

SUBMITTER: Wells AC

PROVIDER: S-EPMC5550279 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells.

Wells Alexandria C AC Daniels Keith A KA Angelou Constance C CC Fagerberg Eric E Burnside Amy S AS Markstein Michele M Alfandari Dominique D Welsh Raymond M RM Pobezinskaya Elena L EL Pobezinsky Leonid A LA

eLife 20170724

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. Decre ...[more]

PMID: 28737488

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