AUTHOR=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. 

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

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01696

DOI=10.3389/fimmu.2017.01696

ISSN=1664-3224

ABSTRACT=<p>We report here that the expression of the transcription factor T-bet, which is known to be required for effector cytotoxic CD8<sup>+</sup> 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<sup>+</sup> T cells is mediated by T-bet. T-bet levels in CTL were controlled <italic>in vivo</italic> by miR-155 <italic>via</italic> 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 <italic>in vivo</italic> CTL responses and suggest an important signaling module that regulates effector CTL immunity.</p>