T cell receptor stimulation impairs IL-7 receptor signaling by inducing expression of the microRNA miR-17 to target Janus kinase 1

Sci Signal. 2014 Aug 26;7(340):ra83. doi: 10.1126/scisignal.2005221.


T cell receptor (TCR)-mediated inhibition of interleukin-7 (IL-7) signaling is important for lineage fate determination in the thymus and for T cell survival in the periphery because uninterrupted IL-7 signaling results in T cell death. The initial event in IL-7 signaling is the transactivation of Janus kinases 1 and 3 (Jak1 and Jak3), which are associated with the cytosolic tails of the IL-7 receptor α chain (IL-7Rα) and the γc subunit, the two cell surface proteins that constitute IL-7R. We found that Jak1 is a highly unstable protein with a half-life of only 1.5 hours, so that continuous Jak1 protein synthesis is required to maintain Jak1 protein in sufficient abundance to support IL-7 signaling. However, we also found that Jak1 protein synthesis was acutely reduced by TCR-responsive microRNAs in the miR-17 family, which targeted Jak1 mRNA (messenger RNA) to inhibit its translation. Thus, this study identifies a molecular mechanism by which TCR engagement acutely disrupts IL-7 signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Immunoprecipitation
  • Janus Kinase 1 / biosynthesis
  • Janus Kinase 1 / genetics*
  • Luciferases
  • Mice
  • MicroRNAs / metabolism*
  • RNA, Messenger / antagonists & inhibitors*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Interleukin-7 / antagonists & inhibitors
  • Receptors, Interleukin-7 / metabolism*
  • Signal Transduction / immunology*


  • MicroRNAs
  • Mirn17 microRNA, mouse
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-7
  • Luciferases
  • Jak1 protein, mouse
  • Janus Kinase 1