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Deltex1 antagonizes HIF-1α and sustains the stability of regulatory T cells in vivo
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346631/ https://www.ncbi.nlm.nih.gov/pubmed/25695215 http://dx.doi.org/10.1038/ncomms7353 |
Sumario: | 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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