The Journal of Immunology · 2011 · 44 citations · 48 references
Life SciencesImmunologyOncologyImmunoregulationMolecular OncologyTumor ProgressionCancer Cell SignalingCancer ProgressionRegulatory T CellsT Cell BiologyT Cell DifferentiationT Cell Responses To TumorsAdaptive Antitumor ImmunityFoxp3 BiologyNuclear Translocation Of Transcription FactorsProtein Tyrosine PhosphorylationT Helper 17 DifferentiationTh17 ResponsesTranscription Factor FamiliesTyrosine Kinase Inhibition
Earlier, we demonstrated the essential role of Kruppel-like transcription factor, TIEG1, in TGF-β-induced regulatory T cell (Treg) development. In this article, we demonstrate that IL-6, which promotes Th17 development, abrogated TIEG1 nuclear translocation and inhibited TGF-β-induced Treg development. Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited TIEG1 nuclear translocation. To test the role of TIEG1-regulated Treg/Th17 development in antitumor immunity, we analyzed TRAMP-C2 tumor growth in TIEG1(-/-) mice. The defective Treg development and elevated Th17 response resulted in enhanced immune reactivity in the tumor and inhibition of TRAMP-C2 tumor growth in TIEG1(-/-) mice. Thus, our results uncovered a novel regulatory mechanism that modulates Tregs and may regulate tumor progression.
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WanJun Chen, Wenwen Jin, Neil J. Hardegen et al. · The Journal of Experimental Medicine · 2003 · 4.6K citations · Full text
TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
Liang Zhou, Jared E. Lopes, Mark M. W. Chong et al. · Nature · 2008 · 1.8K citations