Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation.
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.
Emory Vaccine Center, and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Tuoqi
T
Wu
Andreas
A
Wieland
Koichi
K
Araki
Carl W
CW
Davis
Lilin
L
Ye
J Scott
JS
Hale
Rafi
R
Ahmed
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015536:Down-Regulation; D020868:Gene Silencing; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000235:genetics*; D062085:RNA, Long Noncoding; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases