Journal Article

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

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

2010

Overview

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.

• Publisher: Nature Publishing Group