Article Text

Download PDFPDF

MicroRNA-182 promotes clonal expansion of activated T helper cells
  1. A-B Stittrich,
  2. C Haftmann,
  3. A Hegazy,
  4. M Floessdorf,
  5. J Dong,
  6. F Fuhrmann,
  7. G Heinz,
  8. N Li,
  9. Z Fang,
  10. A Jahn,
  11. R Baumgrass,
  12. J Grün,
  13. W Chen,
  14. T Höfer,
  15. M Löhning,
  16. H-D Chang,
  17. N Rajewsky,
  18. A Radbruch,
  19. M-F Mashreghi
  1. Deutsches Rheuma Forschungszentrum, Germany

Statistics from

Upon activation by antigen, T lymphocytes switch from a resting state to clonal expansion. This switch requires inactivation of the forkhead transcription factor Foxo1, which suppresses proliferation in resting T helper lymphocytes. In the initial antigen-dependent phase of clonal expansion, Foxo1 is inactivated by antigen receptor-dependent post-translational modifications. However, the late antigen-independent phase of clonal expansion is controlled by interleukin 2 (IL2), and it has not been clear how Foxo1 is inactivated in this phase. Here the authors show that in the IL2-dependent late phase of clonal expansion, expression of Foxo1 is downregulated by microRNA-182. Expression of microRNA-182 in activated T lymphocytes is induced by IL2. MicroRNA-182 is expressed between 2 and 4 days after onset of T cell activation. In this time, Foxo1 mRNA expression is reduced by 90%. Specific inhibition of microRNA-182 by locked nucleic acids inhibits clonal expansion of activated T lymphocytes in vitro. Ectopic constitutive expression of microRNA-182 results in a ninefold enhanced clonal expansion in vivo. Our results identify IL2-induced expression of microRNA-182 as a critical step regulating the late phase of clonal expansion of activated T helper lymphocytes, and presumably also the transition from expansion to contraction, as future research may show. The central role of a microRNA, here microRNA-182, in the regulation of T cell expansion provides entirely new options for therapeutic interference, namely the use of specific antagomiRs to limit T cell expansion in vivo. This may be of relevance in immune-mediated diseases.

View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.