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- W4313365874 abstract "Abstract T cells are a critical component of the adaptive immune system and their responses in pathogenic and steady state conditions require strict regulation. One mechanism involved in this regulation is Transforming Growth Factor-β (TGF-β) signaling. TGF-β acts on activated T cells to facilitate the differentiation of some T helper subsets or the suppression of activation and proliferation. Our recent data demonstrate that TGF-β plays a role in the survival of Tregs against continuous antigen exposure. TGF-β signaling is propagated by initially binding to the TGF-β type II receptor, which activates TGF-β type I receptor that phosphorylates the transcription factors SMAD2/SMAD3. This induces nuclear localization of SMAD complexes and transcription of target genes. To understand how TGF-β signaling is coupled to T cell specific events, we generated TGF-βRI deficient Jurkat T cells using the CRISPR/cas9 system. Unexpectedly, TGF-βRI deficient Jurkat demonstrate a hyperactivation phenotype featuring a highly elevated expression of surface antigens (CD69, CD25), and secreted significantly increased levels of IL-2 and TNF. Analysis of signaling events in TGF-βRI deficient Jurkat demonstrate constitutive activity of activator protein-1 (AP-1), constitutive activation of jun-amino-terminal kinase (JNK) and increased expression of JUN. Similarly, in primary T cells transient expression of a dominant negative mutant of TGF-βRI elevated AP-1 activity while a constitutively active mutant reduced this activity. Together, these data show that TGF-βRI signaling plays a novel role in controlling the activity of JNK and AP-1 in T cells. This signaling pathway may play a critical role in TGF-β mediated differentiation and/or survival of T cells." @default.
- W4313365874 created "2023-01-06" @default.
- W4313365874 creator A5022483363 @default.
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- W4313365874 date "2019-05-01" @default.
- W4313365874 modified "2023-09-26" @default.
- W4313365874 title "JNK inhibition by Transforming Growth Factor-β Type I Receptor (TGF-β RI) in T Cells" @default.
- W4313365874 doi "https://doi.org/10.4049/jimmunol.202.supp.184.9" @default.
- W4313365874 hasPublicationYear "2019" @default.
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