title: Deltex1 antagonizes HIF-1α and sustains the stability of regulatory T cells in vivo.
abstract: Application of regulatory T cells (Tregs) in transplantation, autoimmunity and allergy has been extensively explored, but how Foxp3 and Treg stability is regulated in vivo is incompletely understood. Here, we identify a requirement for Deltex1 (DTX1), a contributor to T-cell anergy and Foxp3 protein level maintenance in vivo. Dtx1(-/-) Tregs are as effective as WT Tregs in the inhibition of CD4(+)CD25(-) T-cell activation in vitro. However, the suppressive ability of Dtx1(-/-) Tregs is greatly impaired in vivo. We find that Foxp3 expression is diminished when Dtx1(-/-) Tregs are co-transferred with effector T cells in vivo. DTX1 promotes the degradation of HIF-1α. Knockout of HIF-1α restores the Foxp3 stability and rescues the defective suppressive activity in Dtx1(-/-) Treg cells in vivo. Our results suggest that DTX1 exerts another level of control on Treg stability in vivo by sustaining the expression of Foxp3 protein in Tregs.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, R.O.C.
authors.forename: Huey-Wen
authors.initials: HW
authors.lastname: Hsiao
authors.affiliation: 1] Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, R.O.C [2] Graduate Institute of Immunology, National Taiwan University, Taipei 10057, Taiwan, R.O.C.
authors.forename: Tzu-Sheng
authors.initials: TS
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, R.O.C.
authors.forename: Wen-Hsien
authors.initials: WH
authors.lastname: Liu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, R.O.C.
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Hsieh
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, R.O.C.
authors.forename: Ting-Fang
authors.initials: TF
authors.lastname: Chou
authors.affiliation: 1] Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, R.O.C [2] Graduate Institute of Immunology, National Taiwan University, Taipei 10057, Taiwan, R.O.C.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: National Laboratory Animal Center, National Applied Research Laboratories, Tainan 74147, Taiwan, R.O.C.
authors.forename: Si-Tse
authors.initials: ST
authors.lastname: Jiang
authors.affiliation: 1] Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, R.O.C [2] Graduate Institute of Immunology, National Taiwan University, Taipei 10057, Taiwan, R.O.C.
authors.forename: Ming-Zong
authors.initials: MZ
authors.lastname: Lai
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C104035:Dtx1 protein, mouse; D044767:Ubiquitin-Protein Ligases