Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8 + T-cell differentiation

Tuoqi Wu, Andreas Wieland, Koichi Araki, Carl W. Davis, Lilin Ye, J. Scott Hale, Rafi Ahmed

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

MicroRNAs are important regulators of various developmental and physiological processes. However, their roles in the CD8 + T-cell response are not well understood. Using an acute viral infection model, we show that microRNAs of the miR-17-92 cluster are strongly induced after T-cell activation, down-regulated after clonal expansion, and further silenced during memory development. miR-17-92 promotes cell-cycle progression of effector CD8 +T cells, and its expression is critical to the rapid expansion of these cells. However, excessive miR-17-92 expression enhances mammalian target of rapamycin (mTOR) signaling and strongly skews the differentiation toward short-lived terminal effector cells. Failure to down-regulate miR-17-92 leads to a gradual loss of memory cells and defective central memory cell development. Therefore, our results reveal a temporal expression pattern of miR-17-92 by antigen-specific CD8 + T cells during viral infection, the precise control of which is critical to the effector expansion and memory differentiation of CD8 + T cells.

Original languageEnglish (US)
Pages (from-to)9965-9970
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number25
DOIs
StatePublished - Jun 19 2012
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8 + T-cell differentiation'. Together they form a unique fingerprint.

Cite this