1. MiR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim
- Author
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Gitta Anne Heinz, Nikolaus Rajewsky, Markus Bardua, Hans-Martin Jäck, Marina Backhaus, Anna-Barbara Stittrich, Wei-Wei Chen, Max Löhning, Claudia Haftmann, Jakob Zimmermann, Mareen Matz, Joachim Sieper, Christian Neumann, Joachim R. Grün, Uta Lauer, Kristyna Hradilkova, Alexander Scheffold, Julia Siede, René Riedel, Jürgen Wittmann, Hyun-Dong Chang, Andreas Radbruch, Esther E. Weinberger, Mir-Farzin Mashreghi, Ute Hoffmann, Martina Porstner, Katrin Lehmann, Thomas Häupl, Ria Baumgrass, David Zimmel, Kerstin Westendorf, and Zhuo Fang
- Subjects
Apoptosis ,Arthritis, Rheumatoid ,Th1 ,Twist transcription factor ,Mice ,0302 clinical medicine ,RNA interference ,hemic and lymphatic diseases ,Immunology and Allergy ,RNA, Small Interfering ,Cells, Cultured ,Regulation of gene expression ,Mice, Knockout ,0303 health sciences ,Gene knockdown ,Mice, Inbred BALB C ,Bcl-2-Like Protein 11 ,Nuclear Proteins ,hemic and immune systems ,3. Good health ,Cell biology ,miR-148a ,Bim ,Mir-148a ,T-bet ,Twist1 ,RNA Interference ,medicine.symptom ,Technology Platforms ,biological phenomena, cell phenomena, and immunity ,Molecular Immunology ,Cell Survival ,Immunology ,Inflammation ,chemical and pharmacologic phenomena ,Biology ,03 medical and health sciences ,Downregulation and upregulation ,Proto-Oncogene Proteins ,microRNA ,medicine ,Animals ,Humans ,Transcription factor ,030304 developmental biology ,Twist-Related Protein 1 ,Membrane Proteins ,Th1 Cells ,Molecular biology ,Mice, Inbred C57BL ,MicroRNAs ,Gene Expression Regulation ,Cardiovascular and Metabolic Diseases ,Apoptosis Regulatory Proteins ,T-Box Domain Proteins ,030215 immunology - 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.
- Published
- 2015