Frontiers in Immunology (Dec 2017)

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

  • 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

DOI
https://doi.org/10.3389/fimmu.2017.01696
Journal volume & issue
Vol. 8

Abstract

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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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