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

Mir-Farzin Mashreghi (1) , B. d'Anna (1) , Claudia Haftmann (1) , Evridiki Sgouroudis (1) , Anja Andrea Kühl (1) , Ahmed Nabil Hegazy (1) , Rene Riedel (1) , Michael Flossdorf (1) , Jun Dong (1) , Franziska Fuhrmann (1) , Gitta Anne Heinz (1) , Na Li (1) , Zhuo Fang (1) , Ute Bissels (1) , Farahnaz Hatam (1) , Angelina Jahn (1) , Ben Hammoud (1) , Mareen Matz (1) , Felix-Michael Schulze (1) , Ria Baumgrass (1) , Andreas Bosio (1) , Hans-Joachim Mollenkopf (1) , Joachim R Grün (1) , Andreas Thiel (1) , Wei Chen (1) , Thomas Höfer (1) , Christoph Loddenkemper (1) , Max Löhning (1) , Hyun-Dong Chang (1) , Nikolaus Rajewsky (1) , Andreas Radbruch (1) , Isabel Panse (1)

1 Cell Biology

Upon activation by antigen, helper T lymphocytes switch from a resting state to clonal expansion. This switch requires inactivation of the transcription factor forkhead-box O1 (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 is no longer post-translationally regulated, but is inhibited post-transcriptionally by interleukin-2 (IL-2)-induced microRNA 182 (miR-182). Specific inhibition of miR 182 in helper T lymphocytes limits their 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 up new therapeutic possibilities.

Mots clés: T cells; miRNA

Mir-Farzin Mashreghi, B. d'Anna, Claudia Haftmann, Evridiki Sgouroudis, Anja Andrea Kühl, et al.. MicroRNA-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nature Immunology, 2010, ⟨10.1038/ni.1945⟩. ⟨hal-00584723⟩