Deltex1 antagonizes HIF-1α and sustains the stability of regulatory T cells in vivo.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25695215.
- Also identified by DOI 10.1038/ncomms7353 and PMC identifier 4346631.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- DNA-Binding Proteins
- Forkhead Transcription Factors
- Hypersensitivity
- Hypoxia-Inducible Factor 1, alpha Subunit
- T-Lymphocytes, Regulatory