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

Item Type:Article
Title:Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo
Creators Name:Maschmeyer, P. and Petkau, G. and Siracusa, F. and Zimmermann, J. and Zügel, F. and Kühl, A.A. and Lehmann, K. and Schimmelpfennig, S. and Weber, M. and Haftmann, C. and Riedel, R. and Bardua, M. and Heinz, G.A. and Tran, C.L. and Hoyer, B.F. and Hiepe, F. and Herzog, S. and Wittmann, J. and Rajewsky, N. and Melchers, F.G. and Chang, H.D. and Radbruch, A. and Mashreghi, M.F.
Abstract: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.
Keywords:Inflammatory Bowel Disease, Pro-inflammatory Th1 Cells, Chronic Inflammation, miRNA-148a, Oligonucleotide Therapy, Pre-Clinical Study, Antagomirs, Animals, Mice
Source:Journal of Autoimmunity
Publisher:Elsevier / Academic Press
Page Range:41-52
Date:May 2018
Official Publication:https://doi.org/10.1016/j.jaut.2017.11.005
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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