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miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim

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Item Type:Article
Title:miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim
Creators Name:Haftmann, C. and Stittrich, A.B. and Zimmermann, J. and Fang, Z. and Hradilkova, K. and Bardua, M. and Westendorf, K. and Heinz, G.A. and Riedel, R. and Siede, J. and Lehmann, K. and Weinberger, E.E. and Zimmel, D. and Lauer, U. and Häupl, T. and Sieper, J. and Backhaus, M. and Neumann, C. and Hoffmann, U. and Porstner, M. and Chen, W. and Grün, J.R. and Baumgrass, R. and Matz, M. and Löhning, M. and Scheffold, A. and Wittmann, J. and Chang, H.D. and Rajewsky, N. and Jäck, H.M. and Radbruch, A. and Mashreghi, M.F.
Abstract:Repeatedly activated T helper 1 (Th1) cells present during chronic inflammation can efficiently adapt to the inflammatory milieu, e.g. by expressing the transcription factor Twist1, which limits the immunopathology caused by Th1 cells. Here, we show that in repeatedly reactivated murine Th1 cells, Twist1 and T-bet induce expression of microRNA-148a (miR-148a). miR-148a regulates expression of the proapoptotic gene Bim, resulting in a decreased Bim/Bcl2 ratio. Inhibition of miR-148a by antagomirs in repeatedly reactivated Th1 cells increases the expression of Bim, leading to enhanced apoptosis. Knockdown of Bim expression by siRNA in miR-148a antagomir-treated cells restores viability of the Th1 cells, demonstrating that miR-148a controls survival by regulating Bim expression. Thus, Twist1 and T-bet not only control the differentiation and function of Th1 cells, but also their persistence in chronic inflammation.
Keywords:Bim, miR-148a, T-bet, Twist1, Th1, Animals, Mice
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley-Blackwell (U.S.A.)
Volume:45
Number:4
Page Range:1192-1205
Date:April 2015
Official Publication:https://doi.org/10.1002/eji.201444633
PubMed:View item in PubMed

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