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

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Item Type:	Article
Title:	Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo
Creators Name:	Maschmeyer, P., Petkau, G., Siracusa, F., Zimmermann, J., Zügel, F., Kühl, A.A., Lehmann, K., Schimmelpfennig, S., Weber, M., Haftmann, C., Riedel, R., Bardua, M., Heinz, G.A., Tran, C.L., Hoyer, B.F., Hiepe, F., Herzog, S., Wittmann, J., Rajewsky, N., Melchers, F.G., Chang, H.D., 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
ISSN:	0896-8411
Publisher:	Elsevier / Academic Press
Volume:	89
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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