MiR‐148a is upregulated by Twist1 and T‐bet and promotes Th1‐cell survival by regulating the proapoptotic gene Bim. Issue 4 (22nd January 2015)

• Record Type: Journal Article
• Authors: Haftmann, Claudia; Stittrich, Anna‐Barbara; Zimmermann, Jakob; Fang, Zhuo; Hradilkova, Kristyna; Bardua, Markus; Westendorf, Kerstin; Heinz, Gitta A.; Riedel, René; Siede, Julia; Lehmann, Katrin; Weinberger, Esther E.; Zimmel, David; Lauer, Uta; Häupl, Thomas; Sieper, Joachim; Backhaus, Marina; Neumann, Christian; Hoffmann, Ute; Porstner, Martina; Chen, Wei; Grün, Joachim R; Baumgrass, Ria; Matz, Mareen; Löhning, Max; Scheffold, Alexander; Wittmann, Jürgen; Chang, Hyun‐Dong; Rajewsky, Nikolaus; Jäck, Hans‐Martin; Radbruch, Andreas; Mashreghi, Mir‐Farzin;
• Is Part Of: European journal of immunology. Volume 45:Issue 4(2015:Apr.)
• Page Start: 1192
• Page End: 1205
• Publication Date: 2015-01-22
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201444633
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>Bim</italic>, resulting in a decreased <italic>Bim/Bcl2</italic> ratio. Inhibition of miR‐148a by antagomirs in repeatedly activated Th1 cells increases the expression of Bim, leading to enhanced apoptosis. Knockdown of <italic>Bim</italic> expression by siRNA in miR‐148a antagomir‐treated cells restores viability of the Th1 cells, demonstrating that miR‐148a controls survival by regulating <italic>Bim</italic> expression. Thus, Twist1 and T‐bet not only control the differentiation and function of Th1 cells, but also their persistence in chronic inflammation.</p> </abstract>