Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 45, Issue 4, Pages 1192-1205Publisher
WILEY
DOI: 10.1002/eji.201444633
Keywords
Bim; miR-148a; T-bet; Th1; Twist1
Categories
Funding
- Deutsche Forschungsgemeinschaft [GRK1121, SFB 618, SFB 650, SFB 633, SFB TR52]
- Deutsche Forschungsgemeinschaft (BSRT) [DFG-GSC203]
- International Max Planck Research School for Infectious Diseases and Immunology
- IMI JU [115241]
- FORSYS (Forschungseinheiten zur Systembiologie)
- e:Bio - Innovationswettbewerb Systembiologie program of the Federal Ministry of Education
- Interdisciplinary Center for Clinical Research (IZKF) Erlangen [D7]
- Deutsche Forschungsgemeinschaft (DFG) [GRK1660, FOR832 (JA968/4), TRR130]
- ERC [268987]
- European Research Council (ERC) [268987] Funding Source: European Research Council (ERC)
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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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