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Haftmann, C.* ; Stittrich, A.B.* ; Zimmermann, J.* ; Fang, Z.* ; Hradilkova, K.* ; Bardua, M.* ; Westendorf, K.* ; Heinz, G.A. ; Riedel, R.* ; Siede, J.* ; Lehmann, K.* ; Weinberger, E.E.* ; Zimmel, D.* ; Lauer, U.M.* ; Häupl, T.* ; Sieper, J.* ; Backhaus, M.* ; Neumann, C.* ; Hoffmann, U.* ; Porstner, M.* ; Chen, W.* ; Grün, J.R.* ; Baumgrass, R.* ; Matz, M.* ; Löhning, M.* ; Scheffold, A.* ; Wittmann, J.* ; Chang, H.* ; Rajewsky, N.* ; Jack, H.M.* ; Radbruch, A.H.* ; Mashreghi, M.F.*

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

Eur. J. Immunol. 45, 1192-1205 (2015)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Bim ; Mir-148a ; T-bet ; Th1 ; Twist1; Induced Cell-death; Helper Type-2 Cells; Rheumatoid-arthritis; Th17 Cells; In-vivo; Transcription Factor; Interferon-gamma; Crohns-disease; Lymphocytes; Expression
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Journal European Journal of Immunology
Quellenangaben Volume: 45, Issue: 4, Pages: 1192-1205 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)