Deltex1 antagonizes HIF-1α and sustains the stability of regulatory T cells in vivo

Huey-Wen Hsiao, Tzu-Sheng Hsu, Wen-Hsien Liu, Wan-Chen Hsieh, Ting-Fang Chou, Yu-Jung Wu, Si-Tse Jiang and Ming-Zong Lai ()
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Huey-Wen Hsiao: Institute of Molecular Biology, Academia Sinica
Tzu-Sheng Hsu: Institute of Molecular Biology, Academia Sinica
Wen-Hsien Liu: Institute of Molecular Biology, Academia Sinica
Wan-Chen Hsieh: Institute of Molecular Biology, Academia Sinica
Ting-Fang Chou: Institute of Molecular Biology, Academia Sinica
Yu-Jung Wu: Institute of Molecular Biology, Academia Sinica
Si-Tse Jiang: National Laboratory Animal Center, National Applied Research Laboratories
Ming-Zong Lai: Institute of Molecular Biology, Academia Sinica

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7353

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