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

• Published in: Frontiers in immunology Vol. 8; p. 1696
• Main Authors: Hope, Jennifer L, Stairiker, Christopher J, Spantidea, Panagiota I, Gracias, Donald T, Carey, Alison J, Fike, Adam J, van Meurs, Marjan, Brouwers-Haspels, Inge, Rijsbergen, Laurine C, Fraietta, Joseph A, Mueller, Yvonne M, Klop, Rosemarieke C, Stelekati, Erietta, Wherry, E John, Erkeland, Stefan J, Katsikis, Peter D
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 06-12-2017
• Subjects: CD8+ T cells; Immunology; influenza; MicroRNAs; miR-155; Src homology 2-containing inositol phosphatase-1; T-bet; influenza; CD8+ T cells; Src homology 2-containing inositol phosphatase-1; T-bet; MicroRNAs; miR-155
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2017.01696

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
by miR-155
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
CTL responses and suggest an important signaling module that regulates effector CTL immunity.