TY - JOUR
T1 - Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8 + T-cell differentiation
AU - Wu, Tuoqi
AU - Wieland, Andreas
AU - Araki, Koichi
AU - Davis, Carl W.
AU - Ye, Lilin
AU - Hale, J. Scott
AU - Ahmed, Rafi
PY - 2012/6/19
Y1 - 2012/6/19
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1207327109
DO - 10.1073/pnas.1207327109
M3 - Article
C2 - 22665768
AN - SCOPUS:84862533928
SN - 0027-8424
VL - 109
SP - 9965
EP - 9970
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 25
ER -