The transcription factor T-Bet is regulated by MicroRNA-155 in murine anti-viral CD8+ T cells via SHIP-1
- Hope, Jennifer
- Stairiker, Christopher J.
- Spantidea, P.I. (Panagiota I.)
- Gracias, Donald T.
- Carey, A.J. (Alison J.)
- Fike, Adam J.
- Meurs, Marjan
- Brouwers-Haspels, Inge
- Rijsbergen, L.C. (Laurine C.)
- Fraietta, Joseph A.
- Mueller, Yvonne M.
- Klop, R.C. (Rosemarieke C.)
- Stelekati, E. (Erietta)
- Wherry, E.J. (E.John)
- Erkeland, Stefan
- Katsikis, Peter
DOIAbstract
We report here that the expression of the transcription factor T-bet, which is known to be required for effector cytotoxic CD8+ T lymphocytes (CTL) generation and effector memory cell formation, is regulated in CTL by microRNA-155 (miR-155). Importantly, we show that the proliferative effect of miR-155 on CD8+ T cells is mediated by T-bet. T-bet levels in CTL were controlled in vivo by miR-155 via SH2 (Src homology 2)-containing inositol phosphatase-1 (SHIP-1), a known direct target of miR-155, and SHIP-1 directly downregulated T-bet. Our studies reveal an important and unexpected signaling axis between miR-155, T-bet, and SHIP-1 in in vivo CTL responses and suggest an important signaling module that regulates effector CTL immunity
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