Transcription Factor Smad-Independent T Helper 17 Cell Induction by Transforming-Growth Factor-β Is Mediated by Suppression of Eomesodermin
作者： Kenji Ichiyama , Takashi Sekiya , Naoko Inoue , Taiga Tamiya , Ikko Kashiwagi
DOI: 10.1016/J.IMMUNI.2011.02.021
关键词: SMAD 、 Cellular differentiation 、 Eomesodermin 、 Transcription factor 、 Molecular biology 、 Cell 、 Cell biology 、 Signal transduction 、 Promoter 、 Biology 、 Transforming growth factor
摘要: Transforming growth factor-β (TGF-β) has been shown to be required for Th17 cell differentiation via Smad-independent mechanisms. The molecular mechanism underlying this pathway remains clarified, however. We searched genes regulated by TGF-β through the using Smad2 and Smad3 double-deficient T cells identified transcription factor Eomesodermin (Eomes), whose expression was suppressed c-Jun N-terminal kinase (JNK)-c-Jun signaling pathway. Inhibition of JNK strongly disease in an in vivo EAE model as well in vitro induction. Overexpression Eomes substantially differentiation, whereas ablation could substitute induction primary T cells. Rorc Il17a promoters directly binding proximal region these promoters. In conclusion, suppression is important differentiation.
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