eLife (Jul 2017)

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

  • Alexandria C Wells,
  • Keith A Daniels,
  • Constance C Angelou,
  • Eric Fagerberg,
  • Amy S Burnside,
  • Michele Markstein,
  • Dominique Alfandari,
  • Raymond M Welsh,
  • Elena L Pobezinskaya,
  • Leonid A Pobezinsky

DOI
https://doi.org/10.7554/eLife.26398
Journal volume & issue
Vol. 6

Abstract

Read online

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.

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