Maschmeyer P, Petkau G, Siracusa F, Zimmermann J, Zuegel F, Kuehl AA, Lehmann K, Schimmelpfennig S, Weber M, Haftmann C, Riedel R, Bardua M, Heinz GA, Cam Loan Tran , Hoyer BF, Hiepe F, Herzog S, Wittmann J, Rajewsky N, Melchers FG, Chang HD, Radbruch A, Mashreghi MF (2018)
Publication Type: Journal article
Publication year: 2018
Book Volume: 89
Pages Range: 41-52
DOI: 10.1016/j.jaut.2017.11.005
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.
APA:
Maschmeyer, P., Petkau, G., Siracusa, F., Zimmermann, J., Zuegel, F., Kuehl, A.A.,... Mashreghi, M.-F. (2018). Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo. Journal of Autoimmunity, 89, 41-52. https://dx.doi.org/10.1016/j.jaut.2017.11.005
MLA:
Maschmeyer, Patrick, et al. "Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo." Journal of Autoimmunity 89 (2018): 41-52.
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