miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim
Haftmann C, Stittrich AB, Zimmermann J, Fang Z, Hradilkova K, Bardua M, Westendorf K, Heinz GA, Riedel R, Siede J, Lehmann K, Weinberger EE, Zimmel D, Lauer U, Haeupl T, Sieper J, Backhaus M, Neumann C, Hoffmann U, Porstner M, Chen W, Gruen J, Baumgrass R, Matz M, Loehning M, Scheffold A, Wittmann J, Chang HD, Rajewsky N, Jäck HM, Radbruch A, Mashreghi MF (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 45
Pages Range: 1192-205
Journal Issue: 4
Abstract
Repeatedly activated T helper 1 (Th1) cells present during chronic inflammation can efficiently adapt to the inflammatory milieu, for example, by expressing the transcription factor Twist1, which limits the immunopathology caused by Th1 cells. Here, we show that in repeatedly activated 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 activated 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.
Authors with CRIS profile
Jürgen Wittmann
Department of Molecular Immunology
Hans-Martin Jäck
Department of Molecular Immunology
Involved external institutions
Deutsches Rheuma-Forschungszentrum (DRFZ)
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
How to cite
APA:
Haftmann, C., Stittrich, A.-B., Zimmermann, J., Fang, Z., Hradilkova, K., Bardua, M.,... Mashreghi, M.-F. (2015). miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim. European Journal of Immunology, 45(4), 1192-205. https://doi.org/10.1002/eji.201444633
MLA:
Haftmann, Claudia, et al. "miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim." European Journal of Immunology 45.4 (2015): 1192-205.
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