Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo


  • P. Maschmeyer
  • G. Petkau
  • F. Siracusa
  • J. Zimmermann
  • F. Zügel
  • A.A. Kühl
  • K. Lehmann
  • S. Schimmelpfennig
  • M. Weber
  • C. Haftmann
  • R. Riedel
  • M. Bardua
  • G.A. Heinz
  • C.L. Tran
  • B.F. Hoyer
  • F. Hiepe
  • S. Herzog
  • J. Wittmann
  • N. Rajewsky
  • F.G. Melchers
  • H.D. Chang
  • A. Radbruch
  • M.F. Mashreghi


  • Journal of Autoimmunity


  • J Autoimmun 89: 41-52


  • In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the expression of the pro-apoptotic protein Bim and promotes their survival. Here we use sequence-specific cholesterol-modified oligonucleotides against miR-148a (antagomir-148a) for the selective elimination of pro-inflammatory Th1 cells in vivo. In the murine model of transfer colitis, antagomir-148a treatment reduced the number of pro-inflammatory Th1 cells in the colon of colitic mice by 50% and inhibited miR-148a expression by 71% in the remaining Th1 cells. Expression of Bim protein in colonic Th1 cells was increased. Antagomir-148a-mediated reduction of Th1 cells resulted in a significant amelioration of colitis. The effect of antagomir-148a was selective for chronic inflammation. Antigen-specific memory Th cells that were generated by an acute immune reaction to nitrophenylacetyl-coupled chicken gamma globulin (NP-CGG) were not affected by treatment with antagomir-148a, both during the effector and the memory phase. In addition, antibody titers to NP-CGG were not altered. Thus, antagomir-148a might qualify as an effective drug to selectively deplete pro-inflammatory Th1 cells of chronic inflammation without affecting the protective immunological memory.