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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
European Journal of Immunology
Quellenangaben
Band: 45,
Heft: 4,
Seiten: 1192-1205
Verlag
Wiley
Verlagsort
Hoboken
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Immunology (IMI)