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

Elife. 2017 Jul 24:6:e26398. doi: 10.7554/eLife.26398.

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.

Keywords: CTL; Eomes; Myc; TCR; immunology; metabolism; mouse; naive CD8 T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Differentiation*
  • Mice
  • MicroRNAs / metabolism*

Substances

  • MicroRNAs
  • mirnlet7 microRNA, mouse