miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim
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miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim. / 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.
In: EUR J IMMUNOL, Vol. 45, No. 4, 04.2015, p. 1192-205.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim
AU - Haftmann, Claudia
AU - Stittrich, Anna-Barbara
AU - Zimmermann, Jakob
AU - Fang, Zhuo
AU - Hradilkova, Kristyna
AU - Bardua, Markus
AU - Westendorf, Kerstin
AU - Heinz, Gitta A
AU - Riedel, René
AU - Siede, Julia
AU - Lehmann, Katrin
AU - Weinberger, Esther E
AU - Zimmel, David
AU - Lauer, Uta
AU - Häupl, Thomas
AU - Sieper, Joachim
AU - Backhaus, Marina
AU - Neumann, Christian
AU - Hoffmann, Ute
AU - Porstner, Martina
AU - Chen, Wei
AU - Grün, Joachim R
AU - Baumgrass, Ria
AU - Matz, Mareen
AU - Löhning, Max
AU - Scheffold, Alexander
AU - Wittmann, Jürgen
AU - Chang, Hyun-Dong
AU - Rajewsky, Nikolaus
AU - Jäck, Hans-Martin
AU - Radbruch, Andreas
AU - Mashreghi, Mir-Farzin
N1 - © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/4
Y1 - 2015/4
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis/genetics
KW - Apoptosis Regulatory Proteins/genetics
KW - Arthritis, Rheumatoid/immunology
KW - Bcl-2-Like Protein 11
KW - Cell Survival/immunology
KW - Cells, Cultured
KW - Gene Expression Regulation
KW - Humans
KW - Membrane Proteins/genetics
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - MicroRNAs/antagonists & inhibitors
KW - Nuclear Proteins/genetics
KW - Proto-Oncogene Proteins/genetics
KW - RNA Interference
KW - RNA, Small Interfering
KW - T-Box Domain Proteins/genetics
KW - Th1 Cells/immunology
KW - Twist-Related Protein 1/genetics
U2 - 10.1002/eji.201444633
DO - 10.1002/eji.201444633
M3 - SCORING: Journal article
C2 - 25486906
VL - 45
SP - 1192
EP - 1205
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 4
ER -