|Title:||Deltex1 antagonizes HIF-1 alpha and sustains the stability of regulatory T cells in vivo||Authors:||Hsiao, Huey-Wen
|Issue Date:||2015||Journal Issue:||6||Start page/Pages:||-||Source:||Nat. Commun.||Abstract:||
Application of regulatory Tcells (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 Tcells in vivo. DTX1 promotes the degradation of HIF-1 alpha. Knockout of HIF-1 alpha 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.
|Appears in Collections:||免疫學研究所|
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