The Transcription Factor T-Bet Is Regulated by MicroRNA-155 in Murine Anti-Viral CD8+ T Cells via SHIP-1

oleh: Jennifer L. Hope, Jennifer L. Hope, Christopher J. Stairiker, Christopher J. Stairiker, Panagiota I. Spantidea, Donald T. Gracias, Alison J. Carey, Alison J. Carey, Adam J. Fike, Marjan van Meurs, Inge Brouwers-Haspels, Laurine C. Rijsbergen, Joseph A. Fraietta, Yvonne M. Mueller, Rosemarieke C. Klop, Erietta Stelekati, E. John Wherry, Stefan J. Erkeland, Peter D. Katsikis

Format: Article
Diterbitkan: Frontiers Media S.A. 2017-12-01

Deskripsi

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.