Deltex1 Antagonizes HIF-1α and Sustains the Stability of Regulatory T Cells in Vivo

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Feb 20

PMID 25695215

Citations 35

Authors

Huey-Wen Hsiao

Tzu-Sheng Hsu

Wen-Hsien Liu

Wan-Chen Hsieh

Ting-Fang Chou

Yu-Jung Wu

Si-Tse Jiang

Ming-Zong Lai

Affiliations

Soon will be listed here.

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.

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