The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes.
Stittrich A-B., Haftmann C., Sgouroudis E., Kühl AA., Hegazy AN., Panse I., Riedel R., Flossdorf M., Dong J., Fuhrmann F., Heinz GA., Fang Z., Li N., Bissels U., Hatam F., Jahn A., Hammoud B., Matz M., Schulze F-M., Baumgrass R., Bosio A., Mollenkopf H-J., Grün J., Thiel A., Chen W., Höfer T., Loddenkemper C., Löhning M., Chang H-D., Rajewsky N., Radbruch A., Mashreghi M-F.
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.