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The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes

Authors

  • A.B. Stittrich
  • C. Haftmann
  • E. Sgouroudis
  • A.A. Kuehl
  • A.N. Hegazy
  • I. Panse
  • R. Riedel
  • M. Flossdorf
  • J. Dong
  • F. Fuhrmann
  • G.A. Heinz
  • Z. Fang
  • N. Li
  • U. Bissels
  • F. Hatam
  • A. Jahn
  • B. Hammoud
  • M. Matz
  • F.M. Schulze
  • R. Baumgrass
  • A. Bosio
  • H.J. Mollenkopf
  • J. Gruen
  • A. Thiel
  • W. Chen
  • T. Hoefer
  • C. Loddenkemper
  • M. Loehning
  • H.D. Chang
  • N. Rajewsky
  • A. Radbruch
  • M.F. Mashreghi

Journal

  • Nature Immunology

Citation

  • Nat Immunol 11 (11): 1057-1062

Abstract

  • After being activated by antigen, helper T lymphocytes switch from a resting state to clonal expansion. This switch requires inactivation of the transcription factor Foxo1, a suppressor of proliferation expressed in resting helper T lymphocytes. In the early antigen-dependent phase of expansion, Foxo1 is inactivated by antigen receptor-mediated post-translational modifications. Here we show that in the late phase of expansion, Foxo1 was no longer post-translationally regulated but was inhibited post-transcriptionally by the interleukin 2 (IL-2)-induced microRNA miR-182. Specific inhibition of miR-182 in helper T lymphocytes limited their population expansion in vitro and in vivo. Our results demonstrate a central role for miR-182 in the physiological regulation of IL-2-driven helper T cell-mediated immune responses and open new therapeutic possibilities.


DOI

doi:10.1038/ni.1945